ALBERT

Description:    The isoflavone genistein is used as a pharmacological compound and as a food supplement. The duration and the level of exposure of humans to genistein are considerable. However, the magnitude of genistein-supplemented dietary interventions necessary to induce any changes in the heart has not been studied so far. The aim of this study was to investigate the dose-dependent effects of dietary genistein in the disease- and stress-free mouse heart. Female C57BL/6J mice at the age of 2 months were ovariectomized and randomly assigned to feed on diets with seven different genistein doses (0.01, 0.03, 0.1, 0.3, 1, 3 and 10 g genistein/kg food) for 3 months. Mice with intact ovaries or ovariectomized fed on soy-free diets were used as controls. Ovariectomy led to an increase in body weight, while the two highest genistein doses prevented this increase. Absolute uterus weight was decreased in the ovariectomized group and all genistein groups except for the 10 g/kg food group compared with the intact ovaries/soy-free group. Considering cardiac mass, although the 3 and 10 g/kg food groups had significantly lower absolute heart weight than all other groups, heart-to-body-weight ratios did not differ between these two groups and the intact ovaries/soy-free group, while all remaining groups had smaller ratios. Next, we observed dose-dependent effects of genistein on cardiac gene expression. The present findings indicate that exposure of female mice to the soy isoflavone genistein influences body weight and cardiac mass and gene expression in a dose-dependent manner. Human exposure to dietary genistein supplements may influence cardiac function. Content Type Journal Article Category Research Paper Pages 1-8 DOI 10.1007/s12263-012-0323-5 Authors Ba Tiep Nguyen, Department of Endocrinology, Goettingen University Hospital, Robert-Koch-Str. 40, 37075 Goettingen, Germany Georgios Kararigas, Institute of Gender in Medicine and Center for Cardiovascular Research, Charite University Hospital, Hessische Str. 3-4, 10115 Berlin, Germany Hubertus Jarry, Department of Endocrinology, Goettingen University Hospital, Robert-Koch-Str. 40, 37075 Goettingen, Germany Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description:    Little is known about the role of folate and polymorphisms associated with folate metabolism on prostate cancer risk in populations of African origin. We examined the relationship between serum folate and prostate cancer and whether any association was modified by genetic polymorphisms for folate metabolism. The study was case–control in design and consisted of 218 men 40–80 years old with newly diagnosed, histologically confirmed prostate cancer and 236 cancer-free men attending the same urology clinics in Jamaica, March 2005–July 2007. Serum folate was measured by an immunoassay method and genomic DNA evaluated for MTHR (C677T and A1298C), MTRR A66G, and MTR A2756G polymorphisms. Mean serum folate concentration was higher among cases (12.3 ± 4.1 nmol/L) than controls (9.7 ± 4.2 nmol/L). Serum folate concentration showed a positive association with prostate cancer (OR, 4.41; CI, 2.52–7.72 per 10 nmol/L) regardless of grade. No interactions were observed between genotype and folate concentration, but a weak gene effect was observed for MTHFR A1298C and low-grade prostate cancer. Larger studies to investigate the role of gene–gene/gene–diet interactions in Black men are needed. Content Type Journal Article Category Research Paper Pages 1-9 DOI 10.1007/s12263-012-0321-7 Authors Maria D. Jackson, Department of Community Health and Psychiatry, University of the West Indies, Mona, Kingston 7, Jamaica Marshall K. Tulloch-Reid, Tropical Medicine Research Institute, University of the West Indies, Mona, Kingston, Jamaica Norma McFarlane-Anderson, Department of Basic Medical Sciences, University of the West Indies, Mona Campus, Kingston, Jamaica Alexis Watson, Department Biology, Howard University, Washington, DC, USA Vestra Seers, Department of Biology, Philander Smith College, Little Rock, AR, USA Franklyn I. Bennett, Department of Pathology, University of the West Indies, Mona, Kingston, Jamaica Brian Egleston, Biostatistics and Bioinformatics, Fox Chase Cancer Center, Philadelphia, PA, USA Camille Ragin, Cancer Prevention and Control Program, Fox Chase Cancer Center, Philadelphia, PA, USA Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description:    A methyl-deficient diet (MD) lacking folic acid and the associated methyl donors choline and methionine, fed to the laboratory rat during the periods of oocyte and embryo development, has been shown to programme glucose metabolism in the offspring. The hepatic proteome of the male offspring of female rats fed MD diets for 3 weeks prior to mating and for the first 5 days of gestation has been examined by 2-dimensional gel electrophoresis. Three groups of differentially abundant proteins associated with energy metabolism, amino acid metabolism and antioxidant defence were identified in the soluble proteins extracted from the liver from the MD offspring at both 6 and 12 months of age. Altered mitochondrial activity in other programming models leads to a similar pattern of differential protein abundance. Two of the differentially abundant proteins were identified as GAPDH and PGK-1 by mass spectrometry. Western blotting showed that there were multiple isoforms of both proteins with similar molecular weights but different isoelectric points. The differentially abundant spots reduced in the MD offspring corresponded to minor isoforms of GAPDH and PGK-1. The levels of PPAR-alpha, SREBP and glucocorticoid receptor mRNAs associated with other models of prenatal programming were unchanged in the MD offspring. The data suggest that a diet deficient in folic acid and associated methyl donors fed during the peri-conception and early preimplantation periods of mammalian development affects mitochondrial function in the offspring and that the posttranslational modification of proteins may be important. Content Type Journal Article Category Research Paper Pages 1-10 DOI 10.1007/s12263-012-0314-6 Authors Christopher A. Maloney, School of Medical Sciences, Faculty of Medicine, The University of New South Wales, Sydney, NSW 2052, Australia Susan M. Hay, The Rowett Institute of Nutrition and Health, The University of Aberdeen, Greenburn Road, Bucksburn, Aberdeen, AB21 9SB Scotland, UK Martin D. Reid, The Rowett Institute of Nutrition and Health, The University of Aberdeen, Greenburn Road, Bucksburn, Aberdeen, AB21 9SB Scotland, UK Gary Duncan, The Rowett Institute of Nutrition and Health, The University of Aberdeen, Greenburn Road, Bucksburn, Aberdeen, AB21 9SB Scotland, UK Fergus Nicol, The Rowett Institute of Nutrition and Health, The University of Aberdeen, Greenburn Road, Bucksburn, Aberdeen, AB21 9SB Scotland, UK Kevin D. Sinclair, School of Biosciences, University of Nottingham, Sutton Bonington Campus, Loughborough, Leicestershire, LE12 5RD UK William D. Rees, The Rowett Institute of Nutrition and Health, The University of Aberdeen, Greenburn Road, Bucksburn, Aberdeen, AB21 9SB Scotland, UK Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description:    This commentary is a face-to-face debate between two almost opposite positions regarding the application of genetic engineering in agriculture and food production. Seven questions on the potential benefits of the application of genetic engineering in agriculture and on the potentially adverse impacts on the environment and human health were posed to two scientists: one who is sceptical about the use of GMOs in Agriculture, and one who views GMOs as an important tool for quantitatively and qualitatively improving food production. Content Type Journal Article Category Commentary Pages 1-16 DOI 10.1007/s12263-012-0316-4 Authors M. Buiatti, University of Florence, Florence, Italy P. Christou, Universitat de Lleida - Agrotecnio Center and ICREA, Barcelona, Spain G. Pastore, National Institute for Research on Food and Nutrition, Rome, Italy Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description: S5 TOC Content Type Journal Article Pages 5-5 DOI 10.1007/s12263-011-0266-2 Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932 Journal Volume Volume 6 Journal Issue Volume 6, Supplement 1

Description: Session 3: Sugar transport Content Type Journal Article Pages 25-28 DOI 10.1007/s12263-011-0270-6 Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932 Journal Volume Volume 6 Journal Issue Volume 6, Supplement 1

Description: Poster Presentations Content Type Journal Article Pages 51-81 DOI 10.1007/s12263-011-0277-z Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932 Journal Volume Volume 6 Journal Issue Volume 6, Supplement 1

Description: Session 4: Peptide transport Content Type Journal Article Pages 29-33 DOI 10.1007/s12263-011-0271-5 Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932 Journal Volume Volume 6 Journal Issue Volume 6, Supplement 1

Description: Session 7: Intestinal iron transport Content Type Journal Article Pages 45-47 DOI 10.1007/s12263-011-0274-2 Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932 Journal Volume Volume 6 Journal Issue Volume 6, Supplement 1

Description: Session 5: Intestinal immunology Content Type Journal Article Pages 35-37 DOI 10.1007/s12263-011-0272-4 Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932 Journal Volume Volume 6 Journal Issue Volume 6, Supplement 1

Description: Session 2: intestinal cation transport Content Type Journal Article Pages 19-24 DOI 10.1007/s12263-011-0269-z Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932 Journal Volume Volume 6 Journal Issue Volume 6, Supplement 1

Description: Intestinal physiology amongst the dreaming spires: the 24th EITG meeting, 4–7th September 2011, Oxford, UK Content Type Journal Article Pages 3-4 DOI 10.1007/s12263-011-0265-3 Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932 Journal Volume Volume 6 Journal Issue Volume 6, Supplement 1

Description: Session 6: Amino acid transport Content Type Journal Article Pages 39-43 DOI 10.1007/s12263-011-0273-3 Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932 Journal Volume Volume 6 Journal Issue Volume 6, Supplement 1

Description: Proceeding papers and abstracts Content Type Journal Article Pages 1-1 DOI 10.1007/s12263-011-0264-4 Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932 Journal Volume Volume 6 Journal Issue Volume 6, Supplement 1

Description:    Equol is a daidzein (a phytoestrogen isoflavone) metabolite of gut bacteria, and the ability to produce equol varies between individuals and reduces the risks of several diseases. We tested the effects of equol production on health in Koreans and identified the genetic factors that determine the equol-producing phenotype. In 1391 subjects, the equol-producing phenotype was determined, based on measurements of serum equol concentrations. The anthropometric and blood biochemical measurements between equol producers and nonproducers were analyzed by LC-MS/MS. Genetic factors were identified in a genomewide association study (GWAS), and the interaction between genetic factors and the equol-producing phenotype was examined. We observed that 70.1 % of the study population produced equol. Blood pressure was significantly lower in equol producers (beta ± SE = −1.35 ± 0.67, p  = 0.045). In our genomewide association study, we identified 5 single-nucleotide polymorphisms ( p  〈 1 × 10 −5 ) in HACE1 . The most significant SNP was rs6927608, and individuals with a minor allele of rs6927608 did not produce equol (odds ratio = 0.57 (95 % CI 0.45–0.72), p value = 2.5 × 10 −6 ). Notably, the interaction between equol production and the rs6927608 HACE1 SNP was significantly associated with systolic blood pressure ( p value = 1.3 × 10 4 ). Equol production is linked to blood pressure, and HACE1, identified in our (GWAS), might be a determinant of the equol-producing phenotype. Content Type Journal Article Category Research Paper Pages 1-8 DOI 10.1007/s12263-012-0292-8 Authors Kyung-Won Hong, Division of Epidemiology and Health Index, Center for Genome Science, Korea Centers for Disease Control and Prevention, #187 Osong saengmyeong 2-ro, Gangoe-myeon, Cheongwon-gun, Chungcheongbuk-do, 363-951 Korea Kwang-Pil Ko, Division of Epidemiology and Health Index, Center for Genome Science, Korea Centers for Disease Control and Prevention, #187 Osong saengmyeong 2-ro, Gangoe-myeon, Cheongwon-gun, Chungcheongbuk-do, 363-951 Korea Younjhin Ahn, Division of Epidemiology and Health Index, Center for Genome Science, Korea Centers for Disease Control and Prevention, #187 Osong saengmyeong 2-ro, Gangoe-myeon, Cheongwon-gun, Chungcheongbuk-do, 363-951 Korea Cheong-Sik Kim, Division of Epidemiology and Health Index, Center for Genome Science, Korea Centers for Disease Control and Prevention, #187 Osong saengmyeong 2-ro, Gangoe-myeon, Cheongwon-gun, Chungcheongbuk-do, 363-951 Korea Seon-Joo Park, Division of Epidemiology and Health Index, Center for Genome Science, Korea Centers for Disease Control and Prevention, #187 Osong saengmyeong 2-ro, Gangoe-myeon, Cheongwon-gun, Chungcheongbuk-do, 363-951 Korea Jae Kyung Park, Division of Epidemiology and Health Index, Center for Genome Science, Korea Centers for Disease Control and Prevention, #187 Osong saengmyeong 2-ro, Gangoe-myeon, Cheongwon-gun, Chungcheongbuk-do, 363-951 Korea Sung Soo Kim, Division of Epidemiology and Health Index, Center for Genome Science, Korea Centers for Disease Control and Prevention, #187 Osong saengmyeong 2-ro, Gangoe-myeon, Cheongwon-gun, Chungcheongbuk-do, 363-951 Korea Yeonjung Kim, Division of Epidemiology and Health Index, Center for Genome Science, Korea Centers for Disease Control and Prevention, #187 Osong saengmyeong 2-ro, Gangoe-myeon, Cheongwon-gun, Chungcheongbuk-do, 363-951 Korea Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description: Opening talk Content Type Journal Article Pages 7-11 DOI 10.1007/s12263-011-0267-1 Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932 Journal Volume Volume 6 Journal Issue Volume 6, Supplement 1

Description: Session 8: Fatty acid and vitamin transport Content Type Journal Article Pages 49-50 DOI 10.1007/s12263-011-0275-1 Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932 Journal Volume Volume 6 Journal Issue Volume 6, Supplement 1

Description: Session 1 : colonic physiology Content Type Journal Article Pages 13-17 DOI 10.1007/s12263-011-0268-0 Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932 Journal Volume Volume 6 Journal Issue Volume 6, Supplement 1

Description:    Malnutrition is a prevalent and entrenched global socioeconomic challenge that reflects the combined impact of poverty, poor access to food, inefficient food distribution infrastructure, and an over-reliance on subsistence mono-agriculture. The dependence on staple cereals lacking many essential nutrients means that malnutrition is endemic in developing countries. Most individuals lack diverse diets and are therefore exposed to nutrient deficiencies. Plant biotechnology could play a major role in combating malnutrition through the engineering of nutritionally enhanced crops. In this article, we discuss different approaches that can enhance the nutritional content of staple crops by genetic engineering (GE) as well as the functionality and safety assessments required before nutritionally enhanced GE crops can be deployed in the field. We also consider major constraints that hinder the adoption of GE technology at different levels and suggest policies that could be adopted to accelerate the deployment of nutritionally enhanced GE crops within a multicomponent strategy to combat malnutrition. Content Type Journal Article Category Review Pages 1-13 DOI 10.1007/s12263-012-0315-5 Authors Eduard Pérez-Massot, Department of Plant Production and Forestry Science, ETSEA, University of Lleida-Agrotecnio Center, Av. Alcalde Rovira Roure, 191, 25198 Lleida, Spain Raviraj Banakar, Department of Plant Production and Forestry Science, ETSEA, University of Lleida-Agrotecnio Center, Av. Alcalde Rovira Roure, 191, 25198 Lleida, Spain Sonia Gómez-Galera, Department of Plant Production and Forestry Science, ETSEA, University of Lleida-Agrotecnio Center, Av. Alcalde Rovira Roure, 191, 25198 Lleida, Spain Uxue Zorrilla-López, Department of Plant Production and Forestry Science, ETSEA, University of Lleida-Agrotecnio Center, Av. Alcalde Rovira Roure, 191, 25198 Lleida, Spain Georgina Sanahuja, Department of Plant Production and Forestry Science, ETSEA, University of Lleida-Agrotecnio Center, Av. Alcalde Rovira Roure, 191, 25198 Lleida, Spain Gemma Arjó, Department of Medicine, University of Lleida, Lleida, Spain Bruna Miralpeix, Department of Plant Production and Forestry Science, ETSEA, University of Lleida-Agrotecnio Center, Av. Alcalde Rovira Roure, 191, 25198 Lleida, Spain Evangelia Vamvaka, Department of Plant Production and Forestry Science, ETSEA, University of Lleida-Agrotecnio Center, Av. Alcalde Rovira Roure, 191, 25198 Lleida, Spain Gemma Farré, Department of Plant Production and Forestry Science, ETSEA, University of Lleida-Agrotecnio Center, Av. Alcalde Rovira Roure, 191, 25198 Lleida, Spain Sol Maiam Rivera, Chemistry Department, ETSEA, University of Lleida, 25198 Lleida, Spain Svetlana Dashevskaya, Department of Plant Production and Forestry Science, ETSEA, University of Lleida-Agrotecnio Center, Av. Alcalde Rovira Roure, 191, 25198 Lleida, Spain Judit Berman, Department of Plant Production and Forestry Science, ETSEA, University of Lleida-Agrotecnio Center, Av. Alcalde Rovira Roure, 191, 25198 Lleida, Spain Maite Sabalza, Department of Plant Production and Forestry Science, ETSEA, University of Lleida-Agrotecnio Center, Av. Alcalde Rovira Roure, 191, 25198 Lleida, Spain Dawei Yuan, Department of Plant Production and Forestry Science, ETSEA, University of Lleida-Agrotecnio Center, Av. Alcalde Rovira Roure, 191, 25198 Lleida, Spain Chao Bai, Department of Plant Production and Forestry Science, ETSEA, University of Lleida-Agrotecnio Center, Av. Alcalde Rovira Roure, 191, 25198 Lleida, Spain Ludovic Bassie, Department of Plant Production and Forestry Science, ETSEA, University of Lleida-Agrotecnio Center, Av. Alcalde Rovira Roure, 191, 25198 Lleida, Spain Richard M. Twyman, Department of Biological Sciences, University of Warwick, Coventry, CV4 7AL UK Teresa Capell, Department of Plant Production and Forestry Science, ETSEA, University of Lleida-Agrotecnio Center, Av. Alcalde Rovira Roure, 191, 25198 Lleida, Spain Paul Christou, Department of Plant Production and Forestry Science, ETSEA, University of Lleida-Agrotecnio Center, Av. Alcalde Rovira Roure, 191, 25198 Lleida, Spain Changfu Zhu, Department of Plant Production and Forestry Science, ETSEA, University of Lleida-Agrotecnio Center, Av. Alcalde Rovira Roure, 191, 25198 Lleida, Spain Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description:    In this work, the effect of rosemary extracts rich on polyphenols obtained using pressurized fluids was investigated on the gene expression of human SW480 and HT29 colon cancer cells. The application of transcriptomic profiling and functional enrichment analysis was done via two computational approaches, Ingenuity Pathway Analysis and Gene Set Enrichment Analysis. These two approaches were used for functional enrichment analysis as a previous step for a reliable interpretation of the data obtained from microarray analysis. Reverse transcription quantitative-PCR was used to confirm relative changes in mRNA levels of selected genes from microarrays. The selection of genes was based on their expression change, adjusted p value, and known biological function. According to genome-wide transcriptomics analysis, rosemary polyphenols altered the expression of ~4 % of the genes covered by the Affymetrix Human Gene 1.0ST chip in both colon cancer cells. However, only ~18 % of the differentially expressed genes were common to both cell lines, indicating markedly different expression profiles in response to the treatment. Differences in induction of G2/M arrest observed by rosemary polyphenols in the two colon adenocarcinoma cell lines suggest that the extract may be differentially effective against tumors with specific mutational pattern. From our results, it is also concluded that rosemary polyphenols induced a low degree of apoptosis indicating that other multiple signaling pathways may contribute to colon cancer cell death. Content Type Journal Article Category Research Paper Pages 1-18 DOI 10.1007/s12263-012-0311-9 Authors Alberto Valdés, Laboratory of Foodomics, CIAL (CSIC), Nicolas Cabrera 9, 28049 Madrid, Spain Virginia García-Cañas, Laboratory of Foodomics, CIAL (CSIC), Nicolas Cabrera 9, 28049 Madrid, Spain Lourdes Rocamora-Reverte, Institute of Molecular and Cellular Biology, Miguel Hernandez University, Avda. Universidad s/n, 03202 Elche, Alicante, Spain Ángeles Gómez-Martínez, Institute of Molecular and Cellular Biology, Miguel Hernandez University, Avda. Universidad s/n, 03202 Elche, Alicante, Spain José Antonio Ferragut, Institute of Molecular and Cellular Biology, Miguel Hernandez University, Avda. Universidad s/n, 03202 Elche, Alicante, Spain Alejandro Cifuentes, Laboratory of Foodomics, CIAL (CSIC), Nicolas Cabrera 9, 28049 Madrid, Spain Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description:    Folate hydrolase 1 ( FOLH1 ) gene encodes intestinal folate hydrolase, which regulates intestinal absorption of dietary folate. Previous studies on the association between polymorphisms rs202676 and rs61886492 and the risk of neural tube defects (NTDs) were inconclusive. A case–control study of women with NTD-affected pregnancies ( n  = 160) and controls ( n  = 320) was conducted in the Chinese population of Lvliang, a high-risk area for NTDs. We genotyped the polymorphic sites rs202676 and rs61886492 and assessed maternal plasma folate and total homocysteine (tHcy). Our results showed that in case group, plasma folate concentrations were 18 % lower compared with those of control group (8.32 vs. 6.79 nmol/L, p  = 0.033) and tHcy concentrations were 17 % higher (10.47 vs. 12.65 μmol/L, p  = 0.047). Almost all samples had the rs61886492 GG genotype (99.78 %). The result showed that the frequency of GG genotype in rs202676 was significantly higher in group with multiple NTDs than in controls ( p  = 0.030, OR = 2.157, 95 % CI, 1.06–4.38). The multiple-NTD group showed higher maternal plasma concentrations of tHcy (10.47 vs. 13.96 μmol/L, p  = 0.024). The GG genotype of rs202676 had a lower maternal folate and higher tHcy concentrations than other genotypes with no significant differences. The result of structural prediction indicated that this variation might change the spatial structure of the protein. These results suggested that the maternal polymorphism rs202676 was a potential risk factor for multiple NTDs in this Chinese population. The allele G might affect maternal plasma folate and tHcy concentration. Content Type Journal Article Category Research Paper Pages 1-7 DOI 10.1007/s12263-012-0309-3 Authors Jin Guo, Capital Institute of Pediatrics, Beijing, 100020 People’s Republic of China Hua Xie, Capital Institute of Pediatrics, Beijing, 100020 People’s Republic of China Jianhua Wang, Capital Institute of Pediatrics, Beijing, 100020 People’s Republic of China Huizhi Zhao, Capital Institute of Pediatrics, Beijing, 100020 People’s Republic of China Fang Wang, Capital Institute of Pediatrics, Beijing, 100020 People’s Republic of China Chi Liu, Capital Institute of Pediatrics, Beijing, 100020 People’s Republic of China Li Wang, Capital Institute of Pediatrics, Beijing, 100020 People’s Republic of China Xiaolin Lu, Capital Institute of Pediatrics, Beijing, 100020 People’s Republic of China Yihua Bao, Capital Institute of Pediatrics, Beijing, 100020 People’s Republic of China Jizhen Zou, Capital Institute of Pediatrics, Beijing, 100020 People’s Republic of China Guoliang Wang, Capital Institute of Pediatrics, Beijing, 100020 People’s Republic of China Bo Niu, Department of Molecular Immunology, Capital Institute of Pediatrics No. 2, Yabao Road, Chaoyang District, Beijing, 100020 China Ting Zhang, Capital Institute of Pediatrics, Beijing, 100020 People’s Republic of China Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description:    In the past 20 years, the scientific community has faced a great development in different fields due to the development of high-throughput, omics technologies. Starting from the four major types of omics measurements (genomics, transcriptomics, proteomics, and metabolomics), a variety of omics subdisciplines (epigenomics, lipidomics, interactomics, metallomics, diseasomics, etc.) has emerged. Thanks to the omics approach, researchers are now facing the possibility of connecting food components, foods, the diet, the individual, the health, and the diseases, but this broad vision needs not only the application of advanced technologies, but mainly the ability of looking at the problem with a different approach, a “ foodomics approach”. Foodomics is the comprehensive, high-throughput approach for the exploitation of food science in the light of an improvement of human nutrition. Foodomics is a new approach to food and nutrition that studies the food domain as a whole with the nutrition domain to reach the main objective, the optimization of human health and well-being. Content Type Journal Article Category Commentary Pages 1-4 DOI 10.1007/s12263-012-0310-x Authors Francesco Capozzi, Department of Food Sciences, University of Bologna, Piazza Goidanich, 60, 47521 Cesena, FC, Italy Alessandra Bordoni, Department of Food Sciences, University of Bologna, Piazza Goidanich, 60, 47521 Cesena, FC, Italy Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description:    Nutritional advice has mainly focused on population-level recommendations. Recent developments in nutrition, communication, and marketing sciences have enabled potential deviations from this dominant business model in the direction of personalisation of nutrition advice. Such personalisation efforts can take on many forms, but these have in common that they can only be effective if they are supported by a viable business model. The present paper takes an inventory of approaches to personalised nutrition currently available in the market place as its starting point to arrive at an identification of their underlying business models. This analysis is presented as a unifying framework against which the potential of nutrigenomics-based personalised advice can be assessed. It has uncovered nine archetypical approaches to personalised nutrition advice in terms of their dominant underlying business models. Differentiating features among such business models are the type of information that is used as a basis for personalisation, the definition of the target group, the communication channels that are being adopted, and the partnerships that are built as a part of the business model. Future research should explore the consumer responses to the diversity of “archetypical” business models for personalised nutrition advice as a source of market information on which the delivery of nutrigenomics-based personalised nutrition advice may further build. Content Type Journal Article Category Commentary Pages 1-11 DOI 10.1007/s12263-012-0308-4 Authors Amber Ronteltap, LEI, Part of Wageningen University and Research Centre, Hollandseweg 1, 6706 KN Wageningen, The Netherlands Hans van Trijp, Marketing and Consumer Behaviour Group, Wageningen University and Research Centre, Hollandseweg 1, 6706 KN Wageningen, The Netherlands Aleksandra Berezowska, Marketing and Consumer Behaviour Group, Wageningen University and Research Centre, Hollandseweg 1, 6706 KN Wageningen, The Netherlands Jo Goossens, Bio-Sense, New Business Development, Elisabethlaan 68, 3200 Aarschot, Belgium Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description:    The relationship between obesity and a single nucleotide polymorphism (SNP), rs5443 (C825T), in the guanine nucleotide binding protein beta polypeptide 3 ( GNB3 ) gene is currently inconsistent. In this study, we aimed to reassess whether the GNB3 rs5443 SNP could influence obesity and obesity-related metabolic traits in a Taiwanese population. A total of 983 Taiwanese subjects with general health examinations were genotyped. Based on the criteria defined by the Department of Health in Taiwan, the terms “overweight” and “obesity” are defined as 24 ≦ BMI 〈 27 and BMI ≧ 27, respectively. Compared to the carrier of the combined CT + TT genotypes of the GNB3 rs5443 polymorphism, triglyceride was significantly higher for the carrier of CC genotype in the complete sample population (128.2 ± 93.2 vs. 114.3 ± 79.1 mg/dl; P  = 0.041). In addition, the carriers of CC variant had a higher total cholesterol than those with the combined CT + TT variants (194.5 ± 36.8 vs. 187.9 ± 33.0 mg/dl; P  = 0.019) in the complete sample population. In the normal controls, both triglyceride ( P  = 0.018) and total cholesterol ( P  = 0.011) were also significantly higher in the CC homozygotes than in the combined CT + TT genotypes. However, the GNB3 rs5443 SNP did not exhibit any significant association with obesity or overweight among the subjects. Our study indicates that the CC genotype of the GNB3 rs5443 SNP may predict higher obesity-related metabolic traits such as triglyceride and total cholesterol in non-obese Taiwanese subjects (but not in obese subjects). Content Type Journal Article Category Research Paper Pages 1-8 DOI 10.1007/s12263-012-0304-8 Authors Tun-Jen Hsiao, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan Yuchi Hwang, Vita Genomics, Inc, 7 Fl., No. 6, Sec. 1, Jung-Shing Road, Wugu Shiang, Taipei, Taiwan Can-Hong Liu, Center for Obesity, Taipei Medical University Hospital, Taipei, Taiwan Hua-Mei Chang, Vita Genomics, Inc, 7 Fl., No. 6, Sec. 1, Jung-Shing Road, Wugu Shiang, Taipei, Taiwan Eugene Lin, Vita Genomics, Inc, 7 Fl., No. 6, Sec. 1, Jung-Shing Road, Wugu Shiang, Taipei, Taiwan Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description:    Folic acid is an essential nutrient that is required for one-carbon biosynthetic processes and for methylation of biomolecules. Deficiency of this micronutrient leads to disturbances in normal physiology of cell. Chronic alcoholism is well known to be associated with folate deficiency, which is due in part to folate malabsorption. The present study deals with the regulatory mechanisms of folate uptake in liver during chronic alcoholism. Male Wistar rats were fed 1 g/kg body weight/day ethanol (20 % solution) orally for 3 months, and the molecular mechanisms of folate uptake were studied in liver. The characterization of the folate transport system in liver basolateral membrane (BLM) suggested it to be a carrier mediated and acidic pH dependent, with the major involvement of proton coupled folate transporter and folate binding protein in the uptake. The folate transporters were found to be associated with lipid raft microdomain of liver BLM. Moreover, ethanol ingestion decreased the folate transport by altering the V max of folate transport process and downregulated the expression of folate transporters in lipid rafts. The decreased transporter levels were associated with reduced protein and mRNA levels of these transporters in liver. The deranged folate uptake together with reduced folate transporter levels in lipid rafts resulted in reduced folate levels in liver and thereby to its reduced levels in serum of ethanol-fed rats. The chronic ethanol ingestion led to decreased folate uptake in liver, which was associated with the decreased number of transporter molecules in the lipid rafts that can be ascribed to the reduced synthesis of these transporters. Content Type Journal Article Category Research Paper Pages 1-11 DOI 10.1007/s12263-012-0318-2 Authors Nissar Ahmad Wani, Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012 India Ritambhara Nada, Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012 India Krishan Lal Khanduja, Department of Biophysics, Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012 India Jyotdeep Kaur, Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012 India Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description:    Endothelial hyperpermeability induced by hyperglycemia is the initial step in the development of atherosclerosis, one of the most serious cardiovascular complications in diabetes. In the present study, we investigated the effects of resveratrol (RSV), a bioactive ingredient extracted from Chinese herb rhizoma polygonum cuspidatum , on permeability in vitro and the molecular mechanisms involved. Permeability was assessed by the efflux of fluorescein isothiocyanate (FITC)-dextran permeated through the monolayer endothelial cells (ECs). The mRNA levels, protein expressions, and secretions were measured by quantitative real-time PCR, western blot, and ELISA, respectively. Increased permeability and caveolin-1 (cav-1) expression were observed in monolayer ECs exposed to high glucose. Resveratrol treatment alleviated the hyperpermeability and the overexpression of cav-1 induced by high glucose in a dose-dependent manner. β-Cyclodextrin, a structural inhibitor of caveolae, reduced the hyperpermeability caused by high glucose. Resveratrol also down-regulated the increased expressions of vascular endothelial growth factor (VEGF) and kinase insert domain receptor (KDR, or VEGF receptor-2) induced by high glucose. Inhibition of VEGF/KDR pathway by using SU5416, a selective inhibitor of KDR, alleviated the hyperpermeability and the cav-1 overexpression induced by high glucose. The above results demonstrate that RSV ameliorates caveolae-mediated hyperpermeability induced by high glucose via VEGF/KDR pathway. Content Type Journal Article Category Research Paper Pages 1-9 DOI 10.1007/s12263-012-0319-1 Authors Chong Tian, Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030 People’s Republic of China Rui Zhang, Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030 People’s Republic of China Xiaolei Ye, Department of Public Health, Wenzhou Medical College, Wenzhou, 325035 People’s Republic of China Changhui Zhang, Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030 People’s Republic of China Xin Jin, Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030 People’s Republic of China Yukio Yamori, Institute for World Health Development, Mukogawa Women’s University, Nishinomiya, 663-8179 Japan Liping Hao, Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030 People’s Republic of China Xiufa Sun, Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030 People’s Republic of China Chenjiang Ying, Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030 People’s Republic of China Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description:    Fish aquaculture is considered to be one of the most sustainable sources of protein for humans. Many different species are cultured worldwide, but among them, marine flatfishes comprise a group of teleosts of high commercial interest because of their highly prized white flesh. However, the aquaculture of these fishes is seriously hampered by the scarce knowledge on their biology. In recent years, various experimental ‘omics’ approaches have been applied to farmed flatfishes to increment the genomic resources available. These tools are beginning to identify genetic markers associated with traits of commercial interest, and to unravel the molecular basis of different physiological processes. This article summarizes recent advances in flatfish genomics research in Europe. We focus on the new generation sequencing technologies, which can produce a massive amount of DNA sequencing data, and discuss their potentials and applications for de novo genome sequencing and transcriptome analysis. The relevance of these methods in nutrigenomics and foodomics approaches for the production of healthy animals, as well as high quality and safety products for the consumer, is also briefly discussed. Content Type Journal Article Category Review Pages 1-13 DOI 10.1007/s12263-012-0312-8 Authors Joan Cerdà, Laboratory of Institut de Recerca i Tecnologia Agroalimentàries (IRTA)-Institut de Ciències del Mar, Consejo Superior de Investigaciones Científicas (CSIC), 08003 Barcelona, Spain Manuel Manchado, IFAPA Centro El Toruño, Junta de Andalucía, 11500 El Puerto de Santa María (Cádiz), Spain Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description:    Adult-type hypolactasia (AtH or lactase non-persistence) is the physiological decline in lactase activity that manifests in majority of the world’s population after weaning. Recently, various single-nucleotide polymorphisms (SNPs) upstream of lactase gene ( LCT ) have been suggested to be associated with AtH or the lactase persistent trait in different human populations. C/T -13910 SNP was found be completely associated with AtH in Finnish population, and G/A -22018 SNP was found to be strongly, but not completely, associated with AtH. The aim of this study was to correlate G/A -22018 SNP with intestinal lactase activity in North Indian children. These children were also genotyped for C/T -13910 SNP. We also examined the differences in milk consumption and milk-related clinical symptoms in children with different genotypes of G/A -22018 and C/T -13910 SNPs. Intestinal biopsies were obtained from 231 children aged 2–16 years undergoing routine endoscopy for various abdominal complaints. The biopsies were assayed for lactase, sucrase, and maltase activities and genotyped for G/A -22018 and C/T -13910 SNPs using restriction fragment length polymorphism and DNA sequencing analysis. There was a significant correlation between lactase activity and different genotypes of G/A -22018 SNP. Children with G/G -22018 genotype had low lactase activity. With a reference value of 〈10 U/g protein (lactase activity) to be indicative of AtH, the sensitivity and specificity of genetic test based on G/A -22018 SNP was 94.4 and 94.1 %, respectively. Furthermore, the consumption of milk was lower in children with G/G -22018 genotype. Flatulence was the only symptom significantly more frequent among the children with G/G -22018 genotype compared to those with G/A and A/A -22018 genotypes. However, most of the children with G/G -22018 genotype seem to tolerate small amounts of milk without any significant difference in gastrointestinal symptoms from those with G/A and A/A -22018 genotypes. Content Type Journal Article Category Research Paper Pages 1-7 DOI 10.1007/s12263-012-0305-7 Authors Raja A. H. Kuchay, Department of Experimental Medicine and Biotechnology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012 India Mumtaz Anwar, Department of Experimental Medicine and Biotechnology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012 India Babu R. Thapa, Division of Pediatric Gastroenterology, Hepatology and Nutrition, Postgraduate Institute of Medical Education and Research, Chandigarh, India Akhtar Mahmood, Department of Biochemistry, Panjab University, Chandigarh, India Safrun Mahmood, Department of Experimental Medicine and Biotechnology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012 India Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description: A sideways glance: Lamarck strikes back? Fathers pass on to progeny characteristics they develop during their lives Content Type Journal Article Category Literature Highlights Pages 1-3 DOI 10.1007/s12263-012-0306-6 Authors Sancia Gaetani, INRAN, Via Ardeatina 546, 00178 Rome, Italy Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description:    Dietary polyunsaturated fatty acids (PUFAs) can be converted to prostaglandins and leukotrienes. Oxygenation of omega-6 PUFAs generally results in the production of pro-inflammatory mediators, whereas oxygenated products of omega-3 (n-3) PUFAs generally have lower inflammatory activity. We hypothesize that elevated n-3 PUFA intakes from fish are associated with lower risk of colorectal cancer among those with genetic variants that result in higher levels of pro-inflammatory mediators. In population-based case–control studies of colon (case n  = 1,574) and rectal cancer (case n  = 791) and disease-free controls ( n  = 2,969), we investigated interactions between dietary fatty acid intake and 107 candidate polymorphisms and tagSNPs in PTGS1 , PTGS2 , ALOX12 , ALOX5 , ALOX15 , and FLAP . The two studies used an identical genotyping protocol. We observed interactions and statistically significant increases in colon cancer risk for low docosahexaenoic acid intake among those with the PTGS1 rs10306110 (−1,053 A 〉 G) variant genotypes (OR = 1.6, 95 % confidence interval = 1.1–2.3, adj. p  = 0.06) and rectal cancer risk for low total fat intake among those with the variant PTGS1 rs10306122 (7,135 A 〉 G) (OR vs.wt  = 1.80, 1.02–2.99; adj. p  = 0.08). The ALOX15 rs11568131 (10,339 C 〉 T) wild type in combination with a high inflammation score (low EPA intake, high AA intake, no regular NSAID use, high BMI, smoking) was associated with increased colon cancer risk (OR = 2.28, 1.7–3.07). Rectal cancer risk was inversely associated with a low inflammation score among PTGS2 rs4648276 (3,934 T 〉 C) variant allele carriers (OR = 0.49, 0.25–0.75). Overall, these data provide some modest evidence for interactions between dietary fat intake and genetic variation in genes involved in eicosanoid metabolism and colorectal cancer risk. Content Type Journal Article Category Research Paper Pages 1-12 DOI 10.1007/s12263-012-0302-x Authors Nina Habermann, National Center for Tumor Diseases, Im Neuenheimer Feld 460, 69120 Heidelberg, Germany Cornelia M. Ulrich, National Center for Tumor Diseases, Im Neuenheimer Feld 460, 69120 Heidelberg, Germany Abbie Lundgreen, Department of Medicine, School of Medicine, University of Utah, Salt Lake City, UT 84108, USA Karen W. Makar, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA Elizabeth M. Poole, Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA Bette Caan, Kaiser Permanente Medical Research Program, Department of Research, Oakland, CA 94611, USA Richard Kulmacz, University of Texas Health Science Center at Houston, Houston, TX 77030, USA John Whitton, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA Rachel Galbraith, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA John D. Potter, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA Martha L. Slattery, Department of Medicine, School of Medicine, University of Utah, Salt Lake City, UT 84108, USA Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description:    Significant health benefits have been demonstrated for certain probiotic strains through intervention studies; however, there is a shortage of experimental evidence relative to the mechanisms of action. Here, noninvasive experimental procedure based on a colon organ culture system has been used that, in contrast to most experimental in vitro models reported, can preserve natural immunohistochemical features of the human mucosa. This system has been used to test whether commensal lactobacilli ( Lactobacillus paracasei BL23, Lactobacillus plantarum 299v and L. plantarum 299v (A − )) were able to hinder inflammation-like signals induced by phorbol 12-myristate 13-acetate (PMA)/ionomycin (IO). Whole genome microarrays have been applied to analyze expression differences, from which mRNA markers could be inferred to monitor the effect of putative probiotic strains under such conditions. Regarding the gene expression, PMA/IO treatment induced not only interleukin (IL)-2 and interferon gamma (IFN-γ), as expected, but also other relevant genes related to immune response and inflammation, such as IL-17A, chemokine (C-X-C motif) ligand (CXCL) 9 and CXCL11. The ex vivo culturing did not modify the pattern of expression of those genes or others related to inflammation. Interestingly, this study demonstrated that lactobacilli downregulated those genes and triggered a global change of the transcriptional profile that indicated a clear homeostasis restoring effect and a decrease in signals produced by activated T cells. Content Type Journal Article Category Research Paper Pages 1-16 DOI 10.1007/s12263-012-0301-y Authors Christine Bäuerl, Department of Food Biotechnology, Instituto de Agroquímica y Tecnología de Alimentos, Spanish National Research Council (CSIC), Valencia, Spain Marta Llopis, Digestive System Research Unit, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), University Hospital Vall d’Hebron, Barcelona, Spain María Antolín, Digestive System Research Unit, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), University Hospital Vall d’Hebron, Barcelona, Spain Vicente Monedero, Department of Food Biotechnology, Instituto de Agroquímica y Tecnología de Alimentos, Spanish National Research Council (CSIC), Valencia, Spain Manuel Mata, Research Foundation, Hospital General Universitario, University of Valencia, Valencia, Spain Manuel Zúñiga, Department of Food Biotechnology, Instituto de Agroquímica y Tecnología de Alimentos, Spanish National Research Council (CSIC), Valencia, Spain Francisco Guarner, Digestive System Research Unit, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), University Hospital Vall d’Hebron, Barcelona, Spain Gaspar Pérez Martínez, Department of Food Biotechnology, Instituto de Agroquímica y Tecnología de Alimentos, Spanish National Research Council (CSIC), Valencia, Spain Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description:    The satiating effect of fibre consumption has been related to gut hormones, such as peptide YY and leptin. These peptides may also influence cardiovascular (CVD) risk biomarkers. Nevertheless, there is wide interindividual variation in metabolic responses to fibre consumption. The objective was to investigate differences in the effects of soluble fibre, in the form of Plantago ovata husk (Po-husk) treatment, on CVD risk biomarkers according to selected polymorphisms in genes related to satiety. The study was a multi-centred, double-blind, placebo-controlled, parallel and randomised trial in mild–moderate hypercholesterolaemic patients (age range: 43–67 years). Eight polymorphisms in three genes related to satiety ( LEP , NPY and PYY ) were identified in 178 participants; 88 patients in the placebo (microcrystalline cellulose 14 g/day) group and 90 in the Po-husk (14 g/day) group, which had added to a low-saturated-fat diet for 8 weeks. The CVD biomarkers measured included the following: lipid profile, blood pressure (BP), glucose, insulin, hs-CRP, oxidised LDL and IL-6. Relative to the placebo, Po-husk consumption lowered the plasma total cholesterol concentration by 3.3 % according to rs7799039 polymorphism in the LEP gene ( p  〈 0.05). Furthermore, the Po-husk reduced systolic BP (mean [95 % CI]) by −8 mmHg (−14.16; −1.90) and hs-CRP by 24.9 % in subjects with the AA genotype of the rs16147 polymorphism in the NPY gene (32 % of our total population; p  〈 0.05), which remained significant after Bonferroni correction. In conclusion, polymorphisms in the LEP and NPY genes potentiate the response to Po-husk, particularly the effects on systolic BP and the hs-CRP plasma concentration. Content Type Journal Article Category Research Paper Pages 1-10 DOI 10.1007/s12263-012-0303-9 Authors Anna Crescenti, Departament de Bioquímica i Biotecnologia, Centre Tecnològic de Nutrició i Salut (CTNS), TECNIO, CEICS, Universitat Rovira i Virgili, Campus Sescelades. Marcel·lí Domingo, s/n, 43007 Tarragona, Spain Rosa Solà, Unitat de Recerca en Lípids i Arteriosclerosi, CIBERDEM, Hospital Universitari Sant Joan de Reus, IISPV, Universitat Rovira i Virgili, Reus, Spain Rosa M. Valls, Unitat de Recerca en Lípids i Arteriosclerosi, CIBERDEM, Hospital Universitari Sant Joan de Reus, IISPV, Universitat Rovira i Virgili, Reus, Spain Anna Anguera, Rottapharm\Madaus, S.L., Barcelona, Spain Lluís Arola, Departament de Bioquímica i Biotecnologia, Centre Tecnològic de Nutrició i Salut (CTNS), TECNIO, CEICS, Universitat Rovira i Virgili, Campus Sescelades. Marcel·lí Domingo, s/n, 43007 Tarragona, Spain Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description:    Non-alcoholic fatty liver disease (NAFLD) is one of the first hepatic manifestations of metabolic syndrome, whose progression can lead to cirrhosis and hepatic carcinoma. Interestingly, methyl donor supplementation could improve obesogenic diet-induced hepatic triglyceride accumulation. The aim of this research is to describe methyl donor effects on a high-fat-sucrose (HFS) diet in both sexes and epigenetic changes induced on fatty acid synthase (FASN) promoter methylation pattern as well as gene expression of NAFLD key metabolic genes. Twenty-four male and 28 female Wistar rats were assigned to three dietary groups: control, HFS, and HFS supplemented with methyl donors (choline, betaine, vitamin B12, and folic acid). After 8 weeks of treatment, somatic, biochemical, mRNA, and epigenetic measurements were performed. Rats fed the HFS diet presented an overweight phenotype and alterations in plasma biochemical measurements. Methyl donor supplementation reverted the HFS-diet-induced hepatic triglyceride accumulation. Analysis of FASN promoter cytosine methylation showed changes in both sexes due to the obesogenic diet at −1,096, −780, −778, and −774 CpG sites with respect to the transcriptional start site. Methyl donor supplementation modified DNA methylation at −852, −833, −829, −743, and −733 CpGs depending on the sex. RT-PCR analysis confirmed that FASN expression tended to be altered in males. Our findings reinforce the hypothesis that methyl donor supplementation can prevent hepatic triglyceride accumulation induced by obesogenic diets in both sexes. Changes in liver gene expression profile and epigenetic-mediated mechanisms related to FASN DNA hypermethylation could be involved in methyl donor-induced NAFLD improvement. Content Type Journal Article Category Research Paper Pages 1-9 DOI 10.1007/s12263-012-0300-z Authors P. Cordero, Department of Nutrition and Food Science, Physiology and Toxicology, University of Navarra, 31008 Pamplona, Spain A. M. Gomez-Uriz, Department of Nutrition and Food Science, Physiology and Toxicology, University of Navarra, 31008 Pamplona, Spain J. Campion, Department of Nutrition and Food Science, Physiology and Toxicology, University of Navarra, 31008 Pamplona, Spain F. I. Milagro, Department of Nutrition and Food Science, Physiology and Toxicology, University of Navarra, 31008 Pamplona, Spain J. A. Martinez, Department of Nutrition and Food Science, Physiology and Toxicology, University of Navarra, 31008 Pamplona, Spain Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description:    Nuclear receptors are ligand-activated transcriptional regulators of several key aspects of renal physiology and pathophysiology. As such, nuclear receptors control a large variety of metabolic processes, including kidney lipid metabolism, drug clearance, inflammation, fibrosis, cell differentiation, and oxidative stress. Derangement of nuclear receptor regulation, that is, mainly due to obesity may induce metabolic syndrome, may contribute to the pathogenesis and progression of chronic renal disease and may result in end-stage renal disease. This places nuclear receptors at the forefront of novel therapeutic approaches for a broad range of kidney disorders and diseases, including glomerulosclerosis, tubulointerstitial disease, renal lipotoxicity, kidney fibrosis, and hypertension. This review focuses on the importance of the transcription factors peroxisome proliferator-activated receptor alpha, peroxisome proliferator-activated receptor beta, peroxisome proliferator-activated receptor gamma, liver X receptors, farnesoid X receptor, and the pregnane X receptor/steroid and xenobiotic receptor (PXR) on the physiology and pathophysiology of renal diseases associated with obesity and metabolic syndrome. Content Type Journal Article Category Review Pages 1-16 DOI 10.1007/s12263-012-0295-5 Authors Claudia Tovar-Palacio, Department of Nephrology and Mineral Metabolism, National Medical Science and Nutrition Institute, Salvador Zubirán, Vasco de Quiroga No. 15, Tlalpan, 14000 Mexico, D.F., Mexico Nimbe Torres, Department of Nutrition Physiology, National Medical Science and Nutrition Institute, Salvador Zubirán, Vasco de Quiroga No. 15, Tlalpan, 14000 Mexico, D.F., Mexico Andrea Diaz-Villaseñor, Department of Nutrition Physiology, National Medical Science and Nutrition Institute, Salvador Zubirán, Vasco de Quiroga No. 15, Tlalpan, 14000 Mexico, D.F., Mexico Armando R. Tovar, Department of Nutrition Physiology, National Medical Science and Nutrition Institute, Salvador Zubirán, Vasco de Quiroga No. 15, Tlalpan, 14000 Mexico, D.F., Mexico Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description:    Genetic factors may interact with lifestyle factors to modify obesity risk. FTO and PPARG 2 are relevant obesogenes. Our aim was to explore the effect of Pro12Ala (rs1801282) of PPARG 2 and rs9939609 of FTO on obesity risk and to examine their interaction with lifestyle factors in an elderly population. Subjects ( n  = 978; aged 69 ± 6) were recruited from the SUN (Seguimiento Universidad de Navarra) Project. DNA was obtained from saliva, and lifestyle and dietary data were collected by validated self-reported questionnaires. Genotyping was assessed by RT-PCR plus allele discrimination. Subjects carrying the Ala allele of PPARG 2 gene had a significantly increased obesity risk compared to non-carrier (Pro12Pro) subjects (OR, 1.66; 95  % CI, 1.01–2.74; p  = 0.045). Greater obesity risk was also found in inactive or high carbohydrate intake subjects with the Ala12 allele of PPARG2 gene. Interestingly, subjects carrying the Ala allele of the PPARG 2 gene and with a high CHO (〉246 g/day) intake had an increased obesity risk compared to Pro12Pro subjects (OR, 2.67; 95 % CI, 1.3–5.46; p  = 0.007; p for [CHO ×  PPARG 2] interaction = 0.046). Moreover, in subjects with a high CHO intake, the co-presence of the Ala allele of PPARG2 gene and one minor A allele (rs9939609) of FTO gene did increase obesity risk (OR, 3.26; 95 % CI, 1.19–8.89; p  = 0.021) when compared to non-carrier (Pro12Pro/TT) subjects. In conclusion, it appears that lifestyle factors may act as effect modifiers for obesity risk linked to Ala12 allele of the PPARG 2 gene and the minor A allele of FTO gene in an elderly population. Content Type Journal Article Category Research Paper Pages 1-7 DOI 10.1007/s12263-012-0296-4 Authors Cecilia Galbete, Department of Nutrition, Food Science, Physiology and Toxicology, University of Navarra, C/Irunlarrea s/n, 31008 Pamplona, Navarra, Spain Jon Toledo, Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA, USA Miguel Ángel Martínez-González, Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain J. Alfredo Martínez, Department of Nutrition, Food Science, Physiology and Toxicology, University of Navarra, C/Irunlarrea s/n, 31008 Pamplona, Navarra, Spain Francisco Guillén-Grima, Division of Preventive Medicine, University of Navarra Clinic, Pamplona, Spain Amelia Marti, Department of Nutrition, Food Science, Physiology and Toxicology, University of Navarra, C/Irunlarrea s/n, 31008 Pamplona, Navarra, Spain Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description:    Fatty liver is associated with obesity and breast cancer. We used an obese rat model of mammary cancer to examine whether hepatosteatosis is modifiable by diet and associated with altered expression of hepatic lipogenic enzyme genes, thyroid hormone system genes and cholesterol metabolism-related genes. Beginning at the age of 5 weeks, lean and obese female Zucker rats were fed high-isoflavone soy protein- or casein (control protein)-containing diets. Rats were euthanized at 200 days of age [corresponding to 147 days after administration of carcinogen to induce mammary tumors; (Hakkak et al. in, Oncol Lett 2:29–36, 2011 )]. Obese rats had a greater degree of liver steatosis than lean rats. Obese casein-fed rats had marked steatosis with small foci of mononuclear infiltration, whereas obese soy protein-fed rats had a significantly lower steatosis index. Comparisons between lean and obese casein-fed rats showed that obesity was associated with significant reductions in hepatic mRNA abundance for Glucose 6-Phosphate Dehydrogenase (G6PD), 6-Phosphogluconate Dehydrogenase (6PGD), Thyroid Receptor Alpha 1 (TRα1), Thyroid Receptor Beta 1 (TRβ1) and Iodothyronine Deiodinase 1 (DIO1). The soy protein diet was associated with increased expression of Fatty Acid Synthase (FASN), Malic Enzyme 1 (ME1), 6PGD, Sterol Regulatory Element Binding Protein-1c (SREBP-1c) and SREBP-2 genes in the livers of obese but not lean rats. Western blot analysis showed a significant induction of ME1 protein expression in the livers of obese, soy protein-fed rats, which paralleled the increased serum insulin level in this group. Long-term soy protein consumption can counter hepatic steatosis while coincidently promoting hepatic lipogenic gene expression, the latter likely a consequence of elevated serum insulin. We suggest that elevations in serum insulin, hepatic lipogenesis and cholesterol synthesis all contributed to the increased tumorigenesis previously observed for the obese, soy protein-fed rats. Content Type Journal Article Category Research Paper Pages 1-10 DOI 10.1007/s12263-012-0294-6 Authors Reza Hakkak, Department of Dietetics and Nutrition, University of Arkansas for Medical Sciences, 4301 W. Markham St., Mail Slot 627, Little Rock, AR 72205, USA Ahmed Al-Dwairi, Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, 4301 W. Markham St., #505, Little Rock, AR 72205, USA George J. Fuchs, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA Soheila Korourian, Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA Frank A. Simmen, Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, 4301 W. Markham St., #505, Little Rock, AR 72205, USA Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description:    Conjugated linoleic acid (CLA) is a polyunsaturated fatty acid, which has been recently proven to be effective in reducing body fat mass, but brings as a side effect, the liver enlargement due to an increased lipid content. The in vivo lipogenic activity has been suggested to be due to the reduction in fat mass and to the consequent metabolism of blood glucose to fatty acid in the liver rather than in the adipose tissue. We investigated the ability of CLA to directly induce steatosis by modulating the expression pattern of hepatic proteins involved in lipid metabolism. To avoid interferences derived from CLA metabolism by other tissues, we used the in vitro model of freshly isolated rat hepatocytes incubated in the presence of different CLA isomers. The direct effect of CLA on lipid accumulation in hepatocytes was demonstrated by the altered expression pattern of several proteins involved in lipid metabolism, as assessed by two-dimensional gel electrophoresis and confirmed by Western blotting analysis. The CLA isomer c 9, t 11 was most effective in modulating the protein expression profile. Content Type Journal Article Category Research Paper Pages 1-17 DOI 10.1007/s12263-012-0291-9 Authors E. Rossi, “ProteoWork Lab”, Dipartimento di Scienze Biomediche, Università di Modena e Reggio Emilia, via Campi 287, 41125 Modena, Italy L. Della Casa, “ProteoWork Lab”, Dipartimento di Scienze Biomediche, Università di Modena e Reggio Emilia, via Campi 287, 41125 Modena, Italy S. Piana, Dipartimento di Anatomia Patologica, IRCCS Arcispedale Santa Maria Nuova, 42123 Reggio Emilia, Italy A. Iannone, “ProteoWork Lab”, Dipartimento di Scienze Biomediche, Università di Modena e Reggio Emilia, via Campi 287, 41125 Modena, Italy Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description:    Insulin resistance in skeletal muscle is an early phenomenon in the pathogenesis of type 2 diabetes. Muscle is mainly responsible for insulin-stimulated glucose clearance from the bloodstream. Thus, regulation of gene expression in muscle tissue may be involved in the pathogenesis of insulin resistance. The objective was to investigate gene expression and metabolic pathways alterations in skeletal muscle tissue following an euglycemic-hyperinsulinemic clamp in obese insulin-resistant subjects. We carried out a transcriptome comparison of skeletal muscle tissue before and after a 3-h euglycemic-hyperinsulinemic clamp following 8-week supplementation with n -3 polyunsaturated fatty acid (PUFA) (1.8 g/day) with or without a supplement of fish gelatin (FG) (25 % of daily protein intake) in 16 obese insulin-resistant subjects. Results indicate that approximately 5 % (1932) of expressed transcripts were significantly changed after the clamp in both n -3 PUFA and n -3 PUFA + FG supplementation periods. Of these differentially expressed transcripts, 1394 genes associated with enzymes, transcription and translation regulators, transporters, G protein-coupled receptors, cytokines, and ligand-dependent nuclear receptors were modified. Metabolic pathways that were significantly modified included liver X receptor/retinoid X receptors (RXR) activation, vitamin D receptor/RXR activation, interleukin (IL)-8, acute phase response, IL10, triggering receptor expressed on myeloid cells 1, peroxisome proliferator-activated receptor, G-beta/gamma and hepatocyte growth factor and IL6 signaling. Taken together, results suggest that mainly inflammatory and transcription factors are modified following clamp in obese insulin-resistant subjects. Overall, understanding the changes in metabolic pathways due to insulin may be a potential target for the management of insulin resistance. Content Type Journal Article Category Research Paper Pages 1-8 DOI 10.1007/s12263-012-0298-2 Authors Iwona Rudkowska, Institute of Nutraceuticals and Functional Foods (INAF), Laval University, Pavillon des Services, bureau 2729 K, 2440, boulevard Hochelaga, Québec, QC, G1V 0A6, Canada Hélène Jacques, Institute of Nutraceuticals and Functional Foods (INAF), Laval University, Pavillon des Services, bureau 2729 K, 2440, boulevard Hochelaga, Québec, QC, G1V 0A6, Canada S. John Weisnagel, Department of Medicine, Diabetes Research Unit, Laval University Hospital Research Center, Laval University, Québec, QC, Canada André Marette, Institute of Nutraceuticals and Functional Foods (INAF), Laval University, Pavillon des Services, bureau 2729 K, 2440, boulevard Hochelaga, Québec, QC, G1V 0A6, Canada Marie-Claude Vohl, Institute of Nutraceuticals and Functional Foods (INAF), Laval University, Pavillon des Services, bureau 2729 K, 2440, boulevard Hochelaga, Québec, QC, G1V 0A6, Canada Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description:    TGF-β is a potent pleiotropic factor that promotes small intestinal cell differentiation. The role of microRNAs in the TGF-β induction of intestinal epithelial phenotype is largely unknown. We hypothesized that microRNAs are functionally involved in TGF-β-induced intestinal cell growth. In this study, TGF-β caused a morphological change of IEC-6 cells and stimulated expression of the epithelial cell markers alkaline phosphatase, villin, and aminopeptidase N. By global microRNA profiling during TGF-β-induced intestinal crypt cell (IEC-6) differentiation, we identified 19 differentially expressed microRNAs. We showed by real-time Q-PCR that miR-146b expression increased rapidly after TGF-β treatment; sequence analysis and in vitro assays revealed that miR-146b targets SIAH2, an E3 ubiquitin ligase, with decreased protein expression upon IEC-6 cell differentiation. Transfection of miR-146b inhibitor before TGF-β treatment blocked the down-regulation of SIAH2 in response to TGF-β. Moreover, SIAH2 over-expression during TGF-β treatment caused a significant decrease in Smad7 protein expression in IEC-6 cells. Furthermore, activation of the ERK1/2 pathway is active in the up-regulation of miR-146b by TGF-β. These findings suggest a novel mechanism whereby TGF-β signaling during IEC-6 cell differentiation may be modulated in part by microRNAs, and we propose a key role for miR-146b in the homeostasis of growth factor TGF-β signaling through a negative feedback regulation involving down-regulation of SIAH2 repressed Smad7 activities. Content Type Journal Article Category Research Paper Pages 1-10 DOI 10.1007/s12263-012-0297-3 Authors Yalin Liao, Department of Nutrition, University of California, One Shields Ave., Davis, CA 95616, USA Man Zhang, Department of Nutrition, University of California, One Shields Ave., Davis, CA 95616, USA Bo Lönnerdal, Department of Nutrition, University of California, One Shields Ave., Davis, CA 95616, USA Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description:    It has been established beyond doubt that, as well as the liver, the small intestine is an important site of first-pass metabolism of numerous drugs, food components and toxic xenobiotics. However, there is not much information available about age-dependent changes of intestinal biotransformation pathways. In the present paper, we evaluated the relationships between intestinal cytochrome P450 complex activity and the age of animals . The study was carried out on male Sprague–Dawley rats ( n  = 5) from 5 age series: 0.5-, 2-, 4-, 20-, and 28 months old. Animals at every age series were divided into 4 groups: control and three groups of rats treated with the CYP450 specific inducers: phenobarbital, β-naphtoflavone and dexamethasone, respectively. RNA was isolated from intestinal mucosa, and then standard RT-PCR was used for the analysis of CYP1A1, CYP2B1/2 and CYP3A1 mRNA expression. Additionally, the activities of NADPH-cytochrome P450 and NADH-cytochrome b 5 reductases in the microsomal fraction were biochemically estimated. The constitutive intestinal CYP1A1 mRNA expression changes during maturation and aging. Inducibility of CYP1A1 gene was evident in intestinal mucosa at 2-, 4- and 20-month-old rats. A similar pattern of changes was observed for CYP2B1/2 isoforms. CYP3A1 mRNA expression was not detected in small intestine of 2-week-old rats. In matured rats, constitutive intestinal CYP3A1 expression was low, although after induction, significant increases in CYP3A1 mRNA amount were noted in aged individuals. Intestinal activity of both analyzed reductases was lowest in immature rats and highest in 28-month-old animals. In conclusion, the activity of cytochrome P450 complex in rat small intestine was not decreased by the aging processes, so the high rate of oxidative metabolic reactions in intestinal mucosa can be maintained till the advanced life stage. Content Type Journal Article Category Research Paper Pages 1-11 DOI 10.1007/s12263-011-0240-z Authors Artur Pałasz, Department of Histology, Medical University of Silesia, ul. Medyków 18, 40-752 Katowice, Poland Anna Wiaderkiewicz, Department of Histology, Medical University of Silesia, ul. Medyków 18, 40-752 Katowice, Poland Ryszard Wiaderkiewicz, Department of Histology, Medical University of Silesia, ul. Medyków 18, 40-752 Katowice, Poland Piotr Czekaj, Department of Histology, Medical University of Silesia, ul. Medyków 18, 40-752 Katowice, Poland Beata Czajkowska, Immunology Group, Faculty of Life Sciences, University of Manchester, AV Hill Building, Oxford Road, Manchester, M13 9PT UK Tomasz Lebda-Wyborny, Department of Radiodiagnostics and Nuclear Medicine, Medical University of Silesia, ul. Medyków 14, 40-752 Katowice, Poland Aneta Piwowarczyk, Department of Anatomy, Medical University of Silesia, ul. Medyków 18, 40-752 Katowice, Poland Aleksandra Bryzek, Department of Histology, Medical University of Silesia, ul. Medyków 18, 40-752 Katowice, Poland Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description:    Maternal diet during gestation can exert a long-term effect on the progeny’s health by programming their developmental scheme and metabolism. The aim of this study is to analyze the influence of maternal diet on lipid metabolism in 10- and 16-week-old rats. Pregnant dams were fed one of four diets: a normal protein and normal folic acid diet (NP-NF), a protein-restricted and normal folic acid diet (PR-NF), a protein-restricted and folic-acid-supplemented diet (PR-FS), or a normal protein and folic-acid-supplemented diet (NP-FS). We also tested whether prenatal nutrition determines the reaction of an organism to a postweaning high-fat diet. Blood biochemistry and biometrical parameters were evaluated. The expression patterns of PPARα, PPARγ, and LXRα in the liver and adipose tissue were examined by real-time PCR. In the 10-week-old, rats folic acid supplementation of the maternal diet was associated with reduced circulating glucose and total cholesterol concentrations ( P  〈 0.01 and P  〈 0.001, respectively). Neither prenatal diets nor postnatal feeding affected blood insulin concentrations. In the 16-week-old rats, body weight, abdominal fat mass and central adiposity were reduced in the progeny of the folic acid–supplemented dams ( P  〈 0.01, P  〈 0.001 and P  〈 0.01, respectively). Maternal protein restriction had no effect on biometry or blood biochemical parameters. Folic acid supplementation of the maternal diet was associated with reduced expression of PPARα , PPARγ , and LXRα in the liver ( P  〈 0.001). Reduced protein content in the maternal diet was associated with increased PPARα mRNA level in the liver ( P  〈 0.001) and reduced LXRα in adipose tissue ( P  〈 0.01). PPARα and PPARγ transcription in the liver, as well as LXRα transcription in adipose tissue, was also dependent on interaction effects between prenatal and postnatal diet compositions. PPARγ transcription in the liver was correlated with the abdominal fat mass, body weight, and calorie intake, while PPARγ transcription in adipose tissue was correlated with reduced body weight and calorie intake. Total serum cholesterol concentration was correlated with LXRα transcription in the liver. Folic acid supplementation of the maternal diet may have favorable effects for lipid metabolism in the progeny, but these effects are modified by the postnatal diet and age. Furthermore, the expression of LXRα , PPARα , and PPARγ in the liver and adipose tissue largely depends on the protein and folic acid content in the maternal diet during gestation. However, the altered transcription profile of these key regulators of lipid metabolism does not straightforwardly explain the observed phenotype. Content Type Journal Article Category Research Paper Pages 1-12 DOI 10.1007/s12263-011-0253-7 Authors Agata Chmurzynska, Department of Human Nutrition and Hygiene, Poznań University of Life Sciences, Wojska Polskiego 31, 60-624 Poznań, Poland Monika Stachowiak, Department of Genetics and Animal Breeding, Poznań University of Life Sciences, Poznań, Poland Jan Gawecki, Department of Human Nutrition and Hygiene, Poznań University of Life Sciences, Wojska Polskiego 31, 60-624 Poznań, Poland Ewa Pruszynska-Oszmalek, Department of Animal Physiology and Biochemistry, Poznań University of Life Sciences, Poznań, Poland Małgorzata Tubacka, Department of Human Nutrition and Hygiene, Poznań University of Life Sciences, Wojska Polskiego 31, 60-624 Poznań, Poland Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description:    Genome-wide association studies have identified SNPs reproducibly associated with type 2 diabetes (T2D). We examined the effect of genetic predisposition to T2D on insulin sensitivity and secretion using detailed phenotyping in overweight individuals with no diagnosis of T2D. Furthermore, we investigated whether this genetic predisposition modifies the responses in beta-cell function and insulin sensitivity to a 24-week dietary intervention. We genotyped 25 T2D-associated SNPs in 377 white participants from the RISCK study. Participants underwent an IVGTT prior to and following a dietary intervention that aimed to lower saturated fat intake by replacement with monounsaturated fat or carbohydrate. We composed a genetic predisposition score (T2D-GPS) by summing the T2D risk-increasing alleles of the 25 SNPs and tested for association with insulin secretion and sensitivity at baseline, and with the change in response to the dietary intervention. At baseline, a higher T2D-GPS was associated with lower acute insulin secretion (AIRg 4% lower/risk allele, P  = 0.006) and lower insulin secretion for a given level of insulin sensitivity, assessed by the disposition index (DI 5% lower/risk allele, P  = 0.002), but not with insulin sensitivity (Si). T2D-GPS did not modify changes in insulin secretion, insulin sensitivity or the disposition index in response to the dietary interventions to lower saturated fat. Participants genetically predisposed to T2D have an impaired ability to compensate for peripheral insulin resistance with insulin secretion at baseline, but this does not modify the response to a reduction in dietary saturated fat through iso-energetic replacement with carbohydrate or monounsaturated fat. Content Type Journal Article Category Research Paper Pages 1-8 DOI 10.1007/s12263-012-0284-8 Authors Celia G. Walker, MRC Human Nutrition Research, Elsie Widdowson Laboratory, Fulbourn Road, Cambridge, CB1 9NL UK Ruth J. F. Loos, MRC Epidemiology Unit, Institute of Medical Science, Addenbrooke’s Hospital, Cambridge, UK Adrian P. Mander, MRC Biostatistics Unit Hub for Trials Methodology Research, Institute of Public Health, Cambridge, UK Susan A. Jebb, MRC Human Nutrition Research, Elsie Widdowson Laboratory, Fulbourn Road, Cambridge, CB1 9NL UK Gary S. Frost, Nutrition and Dietetic Research Group, Imperial College London, London, UK Bruce A. Griffin, Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK Julie A. Lovegrove, Hugh Sinclair Unit of Human Nutrition, Institute for Cardiovascular and Metabolic Research (IMCR), University of Reading, Reading, UK Thomas A. B. Sanders, Nutritional Sciences Division, Kings College London, London, UK Les J. Bluck, MRC Human Nutrition Research, Elsie Widdowson Laboratory, Fulbourn Road, Cambridge, CB1 9NL UK Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description:    The fatty-acid-binding protein-2 ( FABP2 ) gene has been proposed as a candidate gene for diabetes because the encoded protein is involved in fatty acid absorption and therefore may affect insulin sensitivity and glucose metabolism. The rare haplotype (B) of its promoter was shown to be associated with a lower risk for type 2 diabetes. The aim of this study was to investigate whether a polymorphism in the FABP2 promoter does affect the metabolic response to either an medium-chain triacylglycerol (MCT) or an long-chain triacylglycerol (LCT) diet, which were suggested to differ in transport mechanisms, in affinity to FABP2 , in activating transcription factors binding to the FABP2 promoter and in their effects on insulin sensitivity. We studied 82 healthy male subjects varying in the FABP2 promoter (42 homozygous for common haplotype (A), 40 homozygous for the rare haplotype (B)) in an interventional study with either an MCT or LCT diet over 2 weeks to examine gene–nutrient interaction. The saturation grade of MCT was adjusted to that of the LCT fat. We determined glucose, insulin, triacylglycerols (TGs), chylomicron triacylglycerols and cholesterol before and after a standardised mixed meal before and after the intervention. HDL cholesterol increased in all groups, which was most pronounced in subjects homozygous for the common promoter haplotype A who received MCT diet ( P  = 0.001), but not significant in homozygous rare haplotype B subjects who received MCT fat. Subjects homozygous for FABP2 haplotype A showed a significant decrease in fasting and postprandial glucose ( P  = 0.01, 0.04, respectively) and a decrease in insulin resistance (HOMA-IR, P  = 0.04) during LCT diet. After correction for multiple testing, those effects did not remain significant. Fasting and postprandial triacylglycerols, LDL cholesterol, chylomicron TGs and cholesterol were not affected by genotype or diet. MCT diet increased HDL cholesterol dependent on the FABP2 promoter haplotype. The effects of the promoter haplotype B could be mediated by PPARγ, which is upregulated by medium-chain fatty acids. Content Type Journal Article Category Research Paper Pages 1-9 DOI 10.1007/s12263-012-0280-z Authors Diana Rubin, Federal Research Centre for Nutrition and Food, Max-Rubner-Institut, Kiel, Germany Ulf Helwig, Federal Research Centre for Nutrition and Food, Max-Rubner-Institut, Kiel, Germany Maria Pfeuffer, Federal Research Centre for Nutrition and Food, Max-Rubner-Institut, Kiel, Germany Annegret Auinger, Federal Research Centre for Nutrition and Food, Max-Rubner-Institut, Kiel, Germany Andreas Ruether, Institute of Clinical Molecular Biology, Christian-Albrechts University, Kiel, Germany Dennis Matusch, Federal Research Centre for Nutrition and Food, Max-Rubner-Institut, Kiel, Germany Stephanie Darabaneanu, Institute for Medical Psychology, University Hospital Schleswig–Holstein, Campus Kiel, Kiel, Germany Sandra Freitag-Wolf, Institute of Medical Informatics and Statistics, University Hospital Schleswig–Holstein, Campus Kiel, Kiel, Germany Michael Nothnagel, Institute of Medical Informatics and Statistics, University Hospital Schleswig–Holstein, Campus Kiel, Kiel, Germany Stefan Schreiber, Department of General Internal Medicine, University Hospital Schleswig–Holstein, Campus Kiel, Kiel, Germany Jürgen Schrezenmeir, Federal Research Centre for Nutrition and Food, Max-Rubner-Institut, Kiel, Germany Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description:    Iron deficiency (ID) remains a public health concern affecting ~25% of the world’s population. Metabolic consequences of ID include elevated plasma glucose concentrations consistent with increased reliance on glucose as a metabolic substrate, though the mechanisms controlling these responses remain unclear. To further characterize the metabolic response to ID, weanling male Sprague–Dawley rats were fed either a control (C; 40 mg Fe/kg diet) or iron-deficient (ID; 3 mg Fe/kg diet) diet or were pair-fed (PF) the C diet to the level of intake of the ID group for 21 days. In addition to reductions in hemoglobin, hematocrit, and plasma iron, the ID group also exhibited higher percent body fat and plasma triglycerides compared to the PF group. Steady-state levels of both plasma glucose and insulin increased 40 and 45%, respectively, in the ID group compared to the PF group. Plasma cortisol levels were decreased 67% in the ID group compared to the PF diet group. The systematic evaluation of the expression of genes involved in insulin signaling, glucose metabolism, and fatty acid metabolism in the liver and skeletal muscle revealed significant alterations in the expression of 48 and 52 genes in these tissues, respectively. A significant concurrent increase in lipogenic gene expression and decrease in gene expression related to β-oxidation in both the liver and skeletal muscle, in combination with differential tissue expression of genes involved in glucose metabolism, provides novel insight into the adaptive metabolic response in rodent models of severe iron deficiency anemia. Content Type Journal Article Category Research Paper Pages 1-11 DOI 10.1007/s12263-011-0278-y Authors McKale R. Davis, Department of Nutritional Sciences, Oklahoma State University, 301 Human Sciences, Stillwater, OK 74078, USA Elizabeth Rendina, Department of Nutritional Sciences, Oklahoma State University, 301 Human Sciences, Stillwater, OK 74078, USA Sandra K. Peterson, Department of Nutritional Sciences, Oklahoma State University, 301 Human Sciences, Stillwater, OK 74078, USA Edralin A. Lucas, Department of Nutritional Sciences, Oklahoma State University, 301 Human Sciences, Stillwater, OK 74078, USA Brenda J. Smith, Department of Nutritional Sciences, Oklahoma State University, 301 Human Sciences, Stillwater, OK 74078, USA Stephen L. Clarke, Department of Nutritional Sciences, Oklahoma State University, 301 Human Sciences, Stillwater, OK 74078, USA Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description:    Selenium (Se) is essential for human health. Despite evidence that Se intake affects inflammatory responses, the mechanisms by which Se and the selenoproteins modulate inflammatory signalling, especially in the gut, are not yet defined. The aim of this work was to assess effects of altered Se supply and knock-down of individual selenoproteins on NF-κB activation in gut epithelial cells. Caco-2 cells were stably transfected with gene constructs expressing luciferase linked either to three upstream NF-κB response elements and a TATA box or only a TATA box. TNFα and flagellin activated NF-κB-dependent luciferase activity and increased IL-8 expression. Se depletion decreased expression of glutathione peroxidase1 ( GPX1 ) and selenoproteins H and W and increased TNFα-stimulated luciferase activity, endogenous IL-8 expression and reactive oxygen species (ROS) production. These effects were not mimicked by independent knock-down of either GPX1 , selenoprotein H or W; indeed, GPX1 knock-down lowered TNFα-induced NF-κB activation and did not affect ROS levels. GPX4 knock-down decreased NF-κB activation by flagellin but not by TNFα. We hypothesise that Se depletion alters the pattern of expression of multiple selenoproteins that in turn increases ROS and modulates NF-κB activation in epithelial cells, but that the effect of GPX1 knock-down is ROS-independent. Content Type Journal Article Category Research Paper Pages 1-12 DOI 10.1007/s12263-011-0256-4 Authors G. Gong, Institute for Cell and Molecular Biosciences, The Medical School, Newcastle University, Framlington Place, Newcastle-upon-Tyne, NE2 4HH UK C. Méplan, Institute for Cell and Molecular Biosciences, The Medical School, Newcastle University, Framlington Place, Newcastle-upon-Tyne, NE2 4HH UK H. Gautrey, Institute for Cell and Molecular Biosciences, The Medical School, Newcastle University, Framlington Place, Newcastle-upon-Tyne, NE2 4HH UK J. Hall, Institute for Cell and Molecular Biosciences, The Medical School, Newcastle University, Framlington Place, Newcastle-upon-Tyne, NE2 4HH UK J. E. Hesketh, Institute for Cell and Molecular Biosciences, The Medical School, Newcastle University, Framlington Place, Newcastle-upon-Tyne, NE2 4HH UK Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description:    Functional polymorphisms in endogenous antioxidant defense genes including manganese superoxide dismutase (MnSOD), catalase (CAT), and glutathione peroxidase (GPX-1) have been linked with risk of cancer at multiple sites. Although it is presumed that these germline variants impact disease risk by altering the host’s ability to detoxify mutagenic reactive oxygen species, very few studies have directly examined this hypothesis. Concentrations of 8-isoprostane F2α (8-iso-PGF2α) and 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxoxdG)—sensitive indicators of lipid peroxidation and DNA oxidation, respectively—were measured in 24-h urine samples obtained from 93 healthy, premenopausal women participating in a dietary intervention trial. In addition, DNA was extracted from blood for genotyping of MnSOD Val16Ala, CAT-262 C 〉 T, and GPX1 Pro198Leu genotypes by Taqman assay. Although geometric mean concentrations of 8-iso-PGF2 α and 8-oxoxdG varied across several study characteristics including race, education level, body mass index, and serum antioxidant levels, there was little evidence that these biomarkers differed across any of the examined genotypes. In summary, functional polymorphisms in endogenous antioxidant defense genes do not appear to be strongly associated with systemic oxidative stress levels in young, healthy women. Content Type Journal Article Category Research Paper Pages 1-5 DOI 10.1007/s12263-011-0257-3 Authors Umaima Al-Alem, Division of Epidemiology and Biostatistics, University of Illinois at Chicago School of Public Health, 1603 W Taylor St., Chicago, IL, USA Peter H. Gann, Department of Pathology, University of Illinois at Chicago College of Medicine, 840 S Wood St, CSN 130, Chicago, IL 60612, USA Jeffrey Dahl, Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago College of Pharmacy, Chicago, IL, USA Richard B. van Breemen, Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago College of Pharmacy, Chicago, IL, USA Vilas Mistry, Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester, UK Patricia M. W. Lam, Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester, UK Mark D. Evans, Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester, UK Linda Van Horn, Department of Preventive Medicine, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA Margaret E. Wright, Department of Pathology, University of Illinois at Chicago College of Medicine, 840 S Wood St, CSN 130, Chicago, IL 60612, USA Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description:    Nonalcoholic fatty liver disease begins with a relatively benign hepatic steatosis, often associated with increased adiposity, but may progress to a more severe nonalcoholic steatohepatitis with inflammation. A subset of these patients develops progressive fibrosis and ultimately cirrhosis. Various dietary components have been shown to contribute to the development of liver disease, including fat, sugars, and neonatal treatment with high doses of monosodium glutamate (MSG). However, rodent models of progressive disease have been disappointing, and alternative animal models of diet-induced liver disease would be desirable, particularly if they contribute to our knowledge of changes in gene expression as a result of dietary manipulation. The domestic cat has previously been shown to be an appropriate model for examining metabolic changes–associated human diseases such as diabetes. Our aim was therefore to compare changes in hepatic gene expression induced by dietary MSG, with that of a diet containing Trans -fat and high fructose corn syrup (HFCS), using a feline model. MSG treatment increased adiposity and promoted hepatic steatosis compared to control ( P  〈 0.05). Exposure to Trans -fat and HFCS promoted hepatic fibrosis and markers of liver dysfunction. Affymetrix microarray analysis of hepatic gene expression showed that dietary MSG promoted the expression of genes involved in cholesterol and steroid metabolism. Conversely, Trans -fat and HFCS feeding promoted the expression of genes involved in lipolysis, glycolysis, liver damage/regeneration, and fibrosis. Our feline model examining gene–diet interactions (nutrigenomics) demonstrates how dietary MSG, Trans -fat, and HFCS may contribute to the development of hepatic steatosis. Content Type Journal Article Category Research Paper Pages 1-16 DOI 10.1007/s12263-011-0261-7 Authors Kate S. Collison, Cell Biology and Diabetes Research Unit, Department of Biological and Medical Research, MBC 03, King Faisal Specialist Hospital and Research Centre, P. O. Box 3354, Riyadh, 11211 Saudi Arabia Marya Z. Zaidi, Cell Biology and Diabetes Research Unit, Department of Biological and Medical Research, MBC 03, King Faisal Specialist Hospital and Research Centre, P. O. Box 3354, Riyadh, 11211 Saudi Arabia Soad M. Saleh, Cell Biology and Diabetes Research Unit, Department of Biological and Medical Research, MBC 03, King Faisal Specialist Hospital and Research Centre, P. O. Box 3354, Riyadh, 11211 Saudi Arabia Nadine J. Makhoul, Cell Biology and Diabetes Research Unit, Department of Biological and Medical Research, MBC 03, King Faisal Specialist Hospital and Research Centre, P. O. Box 3354, Riyadh, 11211 Saudi Arabia Angela Inglis, Cell Biology and Diabetes Research Unit, Department of Biological and Medical Research, MBC 03, King Faisal Specialist Hospital and Research Centre, P. O. Box 3354, Riyadh, 11211 Saudi Arabia Joey Burrows, VivoCore Inc., Toronto, ON, Canada Joseph A. Araujo, VivoCore Inc., Toronto, ON, Canada Futwan A. Al-Mohanna, Cell Biology and Diabetes Research Unit, Department of Biological and Medical Research, MBC 03, King Faisal Specialist Hospital and Research Centre, P. O. Box 3354, Riyadh, 11211 Saudi Arabia Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description:    There is controversy as to the recommended daily intake of selenium (Se), and whether current New Zealand diets are adequate in this nutrient. Various functional single-nucleotide polymorphisms (SNPs) polymorphisms may affect the efficacy of Se utilisation. These include the glutathione peroxidases GPx1 rs1050450, GPx4 rs713041, as well as selenoproteins SEPP1 rs3877899, SEL15 rs5845, SELS rs28665122 and SELS rs4965373. This cross-sectional study measured serum Se levels of 503 healthy Caucasian men in Auckland, New Zealand, between ages 20–81. The Se distribution was compared with activities of the antioxidant enzymes glutathione peroxidase and thioredoxin reductase, and DNA damage as measured by the single cell gel electrophoresis assay, both without and with a peroxide-induced oxidative challenge. Serum Se was measured using inductively coupled plasma-dynamic reaction cell-mass spectrometry, while selenoprotein SNPs were estimated using TaqMan ® SNP genotyping assays. While antioxidant enzyme activities and DNA damage recorded after a peroxide challenge increased with increasing serum selenium, the inherent DNA damage levels in leukocytes showed no statistically significant relationship with serum selenium. However, these relationships and dietary Se requirements at the individual level were modified by several different SNPs in genes for selenoproteins. The GPx1 rs1050450 C allele was significantly associated with GPx activity. Significant correlations between serum Se level and GPX activity were seen with all genotypes except for homozygous minor allele carriers, while the GPx1 rs1050450 CT genotype showed the highest correlation. Several genotypes showed significant correlations between serum Se and TR activity with SEPP1 rs3877899 GG genotype showing the highest correlation. A significant decreasing trend in DNA damage with increasing serum Se was seen among GPx1 rs1050450 CC and GPx4 rs713041 TT genotype carriers up to a serum Se level of 116 and 149 ng/ml, respectively. In the absence of this genetic information, we would recommend a serum Se concentration in the region of 100–150 ng/ml as providing a useful compromise. Content Type Journal Article Category Research Paper Pages 1-12 DOI 10.1007/s12263-011-0259-1 Authors Nishi Karunasinghe, Auckland Cancer Society Research Centre, FM&HS, The University of Auckland, Auckland, New Zealand Dug Yeo Han, Discipline of Nutrition, FM&HS, The University of Auckland, Auckland, New Zealand Shuotun Zhu, Auckland Cancer Society Research Centre, FM&HS, The University of Auckland, Auckland, New Zealand Jie Yu, Discipline of Nutrition, FM&HS, The University of Auckland, Auckland, New Zealand Katja Lange, Discipline of Nutrition, FM&HS, The University of Auckland, Auckland, New Zealand He Duan, Auckland Cancer Society Research Centre, FM&HS, The University of Auckland, Auckland, New Zealand Roxanne Medhora, Discipline of Nutrition, FM&HS, The University of Auckland, Auckland, New Zealand Nabitha Singh, Discipline of Nutrition, FM&HS, The University of Auckland, Auckland, New Zealand James Kan, Discipline of Nutrition, FM&HS, The University of Auckland, Auckland, New Zealand Waseem Alzaher, Discipline of Nutrition, FM&HS, The University of Auckland, Auckland, New Zealand Benson Chen, Discipline of Nutrition, FM&HS, The University of Auckland, Auckland, New Zealand Sarah Ko, Discipline of Nutrition, FM&HS, The University of Auckland, Auckland, New Zealand Christopher M. Triggs, Department of Statistics, Faculty of Science, The University of Auckland, Auckland, New Zealand Lynnette R. Ferguson, Auckland Cancer Society Research Centre, FM&HS, The University of Auckland, Auckland, New Zealand Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description:    Consumption of trans fatty acids is positively correlated with cardiovascular diseases and with atherogenic risk factors. Trans fatty acids might play their atherogenic effects through lipid metabolism alteration of vascular cells. Accumulation of lipids in vascular smooth muscle cells is a feature of atherosclerosis and a consequence of lipid metabolism alteration. Stearoyl-CoA desaturase 1 (scd1) catalyses the production of monounsaturated fatty acids (e.g. oleic acid) and its expression is associated with lipogenesis induction and with atherosclerosis development. We were interested in analysing the regulation of delta-9 desaturation rate and scd1 expression in human aortic smooth muscle cells (HASMC) exposed to cis and trans C18:1 fatty acid isomers ( cis -9 oleic acid, trans -11 vaccenic acid or trans -9 elaidic acid) for 48 h at 100 μM. Treatment of HASMC with these C18:1 fatty acid isomers led to differential effects on delta-9 desaturation; oleic acid repressed the desaturation rate more potently than trans -11 vaccenic acid, whereas trans -9 elaidic acid increased the delta-9 desaturation rate. We then correlated the delta-9 desaturation rate with the expression of scd1 protein and mRNA. We showed that C18:1 fatty acids controlled the expression of scd1 at the transcriptional level in HASMC, leading to an increase in scd1 mRNA content by trans -9 elaidic acid treatment, whereas a decrease in scd1 mRNA content was observed with cis -9 oleic acid and trans -11 vaccenic acid treatments. Altogether, this work highlights a differential capability of C18:1 fatty acid isomers to control scd1 gene expression, which presumes of different consequent effects on cell functions. Content Type Journal Article Category Research Paper Pages 1-8 DOI 10.1007/s12263-011-0258-2 Authors M. Minville-Walz, Université de Bourgogne, Centre de recherche INSERM, UMR866, 6 Boulevard Gabriel, 21000 Dijon, France J. Gresti, Université de Bourgogne, Centre de recherche INSERM, UMR866, 6 Boulevard Gabriel, 21000 Dijon, France L. Pichon, Université de Bourgogne, Centre de recherche INSERM, UMR866, 6 Boulevard Gabriel, 21000 Dijon, France S. Bellenger, Université de Bourgogne, Centre de recherche INSERM, UMR866, 6 Boulevard Gabriel, 21000 Dijon, France J. Bellenger, Université de Bourgogne, Centre de recherche INSERM, UMR866, 6 Boulevard Gabriel, 21000 Dijon, France M. Narce, Université de Bourgogne, Centre de recherche INSERM, UMR866, 6 Boulevard Gabriel, 21000 Dijon, France M. Rialland, Université de Bourgogne, Centre de recherche INSERM, UMR866, 6 Boulevard Gabriel, 21000 Dijon, France Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description:    Experimental replication is fundamental for practicing science. To reduce variability, it is essential to control sources of variation as much as possible. Diet is an important factor that can influence many processes and functional outcomes in studies performed with rodent models. This is especially true for, but not limited to, nutritional studies. To compare functional effects of different nutrients, it is important to use standardized, semi-purified diets. Here, we propose and describe a standard reference diet, the BIOCLAIMS standard diet. The diet is AIN-93 based, but further defined with dietary and experimental requirements taken into account that allow for experiments with bioactive food components and natural (non-expensive) labeling. This diet will be implemented by two European research consortia, Mitofood and BIOCLAIMS, to ensure inter-laboratory comparability. Content Type Journal Article Category Research Paper Pages 1-6 DOI 10.1007/s12263-011-0262-6 Authors Femke P. M. Hoevenaars, Department of Human and Animal Physiology, Wageningen University, Wageningen, The Netherlands Evert M. van Schothorst, Department of Human and Animal Physiology, Wageningen University, Wageningen, The Netherlands Olga Horakova, Department of Adipose Tissue Biology, Institute of Physiology Academy of Sciences of the Czech Republic v.v.i., Prague, Czech Republic Anja Voigt, Group of Energy Metabolism, German Institute of Human Nutrition in Potsdam, Nuthetal, Germany Martin Rossmeisl, Department of Adipose Tissue Biology, Institute of Physiology Academy of Sciences of the Czech Republic v.v.i., Prague, Czech Republic Catalina Pico, Molecular Biology, Nutrition and Biotechnology (Nutrigenomics), University of the Balearic Islands (UIB), Palma de Mallorca, Spain Antoni Caimari, Centre Tecnologic de Nutrició i Salut (CTNS), TECNIO, CEICS, Reus, Spain Jan Kopecky, Department of Adipose Tissue Biology, Institute of Physiology Academy of Sciences of the Czech Republic v.v.i., Prague, Czech Republic Susanne Klaus, Group of Energy Metabolism, German Institute of Human Nutrition in Potsdam, Nuthetal, Germany Jaap Keijer, Department of Human and Animal Physiology, Wageningen University, Wageningen, The Netherlands Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description:    Epidemiological studies have indicated a positive association between the intake of foods rich in anthocyanins and the protection against cardiovascular diseases. Some authors have shown that anthocyanins are degraded by the gut microflora giving rise to the formation of other breakdown metabolites, which could also contribute to anthocyanin health effects. The objective of this study was to evaluate the effects of anthocyanins and their breakdown metabolites, protocatechuic, syringic, gallic, and vanillic acids, on different parameters involved in atherosclerosis, including inflammation, cell adhesion, chemotaxis, endothelial function, estrogenic/anti-estrogenic activity, and angiotensin-converting enzyme (ACE) inhibitory activity. From the assayed metabolites, only protocatechuic acid exhibited a slight inhibitory effect on NO production and TNF-α secretion in LPS-INF-γ-induced macrophages. Gallic acid caused a decrease in the secretion of MCP-1, ICAM-1, and VCAM-1 in endothelial cells. All anthocyanins showed an ACE-inhibitory activity. Delphinidin-3-glucoside, pelargonidin-3-glucoside, and gallic acid showed affinity for ERβ and pelargonidin and peonidin-3-glucosides for ERα. The current data suggest that anthocyanins and their breakdown metabolites may partly provide a protective effect against atherosclerosis that is multi-causal and involves different biochemical pathways. However, the concentrations of anthocyanins and their metabolites, as used in the present cell culture and in vitro assays mediating anti-inflammatory, anti-adhesive, anti-estrogenic, and angiotensin-converting enzyme inhibitory activities, were often manifold higher than those physiologically achievable. Content Type Journal Article Category Research Paper Pages 1-12 DOI 10.1007/s12263-011-0263-5 Authors Maria Hidalgo, Institute of Food Science, Food Technology and Nutrition (ICTAN), Spanish National Research Council (CSIC), Ciudad Universitaria, José Antonio Novais 10, 28040 Madrid, Spain Sonsoles Martin-Santamaria, Department of Chemistry, Facultad de Farmacia, Universidad San Pablo CEU, Boadilla del Monte, 28668 Madrid, Spain Isidra Recio, Instituto de Investigacion en Ciencias de la Alimentacion (CIAL, CSIC-UAM), Campus de la Universidad Autonoma de Madrid, Nicolas Cabrera, 9, 28049 Madrid, Spain Concepcion Sanchez-Moreno, Institute of Food Science, Food Technology and Nutrition (ICTAN), Spanish National Research Council (CSIC), Ciudad Universitaria, José Antonio Novais 10, 28040 Madrid, Spain Beatriz de Pascual-Teresa, Department of Chemistry, Facultad de Farmacia, Universidad San Pablo CEU, Boadilla del Monte, 28668 Madrid, Spain Gerald Rimbach, Institute of Human Nutrition and Food Science, Division of Food Science, Christian-Albrechts-University Kiel, Hermann-Rodewald-Strasse 6, 24118 Kiel, Germany Sonia de Pascual-Teresa, Institute of Food Science, Food Technology and Nutrition (ICTAN), Spanish National Research Council (CSIC), Ciudad Universitaria, José Antonio Novais 10, 28040 Madrid, Spain Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description:    Strategies to prevent and treat obesity aim to decrease energy intake and/or increase energy expenditure. Regarding the increase of energy expenditure, two key intracellular targets may be considered (1) mitochondrial oxidative phosphorylation, the major site of ATP production, and (2) AMP-activated protein kinase (AMPK), the master regulator of cellular energy homeostasis. Experiments performed mainly in transgenic mice revealed a possibility to ameliorate obesity and associated disorders by mitochondrial uncoupling in metabolically relevant tissues, especially in white adipose tissue (WAT), skeletal muscle (SM), and liver. Thus, ectopic expression of brown fat-specific mitochondrial uncoupling protein 1 (UCP1) elicited major metabolic effects both at the cellular/tissue level and at the whole-body level. In addition to expected increases in energy expenditure, surprisingly complex phenotypic effects were detected. The consequences of mitochondrial uncoupling in WAT and SM are not identical, showing robust and stable obesity resistance accompanied by improvement of lipid metabolism in the case of ectopic UCP1 in WAT, while preservation of insulin sensitivity in the context of high-fat feeding represents the major outcome of muscle UCP1 expression. These complex responses could be largely explained by tissue-specific activation of AMPK, triggered by a depression of cellular energy charge. Experimental data support the idea that (1) while being always activated in response to mitochondrial uncoupling and compromised intracellular energy status in general, AMPK could augment energy expenditure and mediate local as well as whole-body effects; and (2) activation of AMPK alone does not lead to induction of energy expenditure and weight reduction. Content Type Journal Article Category Review Pages 1-18 DOI 10.1007/s12263-011-0260-8 Authors Susanne Klaus, German Institute of Human Nutrition, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany Susanne Keipert, German Institute of Human Nutrition, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany Martin Rossmeisl, Department of Adipose Tissue Biology, Institute of Physiology Academy of Sciences of the Czech Republic v.v.i., Videnska 1083, 14220 Prague, Czech Republic Jan Kopecky, Department of Adipose Tissue Biology, Institute of Physiology Academy of Sciences of the Czech Republic v.v.i., Videnska 1083, 14220 Prague, Czech Republic Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description:    There is a need for a tool to assess dietary intake related to the habitual dietary glycaemic index (GI) and fibre in groups with large numbers of individuals. Novel metabolite-profiling techniques may be a useful approach when applied to human urine. In a long-term, controlled dietary intervention study, metabolomics were applied to assess dietary patterns. A targeted approach was used to evaluate the effects on urinary C-peptide excretion caused by the dietary treatments. Seventy-seven overweight subjects followed an 8-week low-calorie diet (LCD) and were then randomly assigned to a high-GI or low-GI diet for 6 month during which they completed 24-h urine collections at baseline (prior to the 8-week LCD) and after randomisation to the dietary intervention, at month 1, 3 and 6, respectively. Metabolite profiling in 24-h urine was performed by 1 H NMR and chemometrics. Partial least squares (PLS) analysis indicated that urinary formate could discriminate between high-GI and low-GI diets (correlation coefficient r  = 0.82), and this finding was confirmed statistically ( P  = 0.01). PLS analysis also indicated that urinary hippurate could be associated with fibre intake, but this finding was not confirmed statistically. No associations between GI and urinary C-peptide were found. Our results emphasise that application of metabolomics is useful in the assessment of dietary exposure related to dietary GI and fibre seen at group level in a nutritional metabolomic study of human urine. As our design allowed for large variations in individually selected food items, biomarkers identified at group level may be interpreted as more general and robust markers, largely not confounded with markers from single dietary factors. Content Type Journal Article Category Research Paper Pages 1-13 DOI 10.1007/s12263-011-0250-x Authors Lone G. Rasmussen, Department of Human Nutrition, Faculty of Life Sciences, University of Copenhagen, Frederiksberg, Denmark Hanne Winning, Foss Analytical A/S, Hillerød, Denmark Francesco Savorani, Quality and Technology, Department of Food Science, Faculty of Life Sciences, University of Copenhagen, Frederiksberg, Denmark Christian Ritz, Department of Basic Sciences and Environment, Faculty of Life Sciences, University of Copenhagen, Frederiksberg, Denmark Søren B. Engelsen, Quality and Technology, Department of Food Science, Faculty of Life Sciences, University of Copenhagen, Frederiksberg, Denmark Arne Astrup, Department of Human Nutrition, Faculty of Life Sciences, University of Copenhagen, Frederiksberg, Denmark Thomas M. Larsen, Department of Human Nutrition, Faculty of Life Sciences, University of Copenhagen, Frederiksberg, Denmark Lars O. Dragsted, Department of Human Nutrition, Faculty of Life Sciences, University of Copenhagen, Frederiksberg, Denmark Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description:    The medicinal properties of the leaves and fruit of Olea Europaea (olive tree) have been known since antiquity. Numerous contemporary studies have linked the Mediterranean diet with increased health. In particular, consumption of olive oil has been associated with a decreased risk of cardiovascular disease and certain cancers. Increasingly, there has been an interest in the biological properties of polyphenols, which are minor constituents of olive oil. For example, hydroxytyrosol has been shown to be a potent antioxidant and has anti-atherogenic and anti-cancer properties. The overall aim of this study was to provide insights into the molecular mechanisms of action of hydroxytyrosol using genome-wide mRNA-Seq. Initial experiments were aimed at assessing cytotoxicity, apoptosis and cell cycle effects of hydroxytyrosol in various cell lines. The findings indicated a dose-dependent reduction in cell viability in human erythroleukemic K562 and human keratinocytes. When comparing the viability in parental CEM-CCRF and R100 cells (which overexpress the P-glycoprotein pump), it was determined that the R100 cells were more resistant to effects of hydroxytyrosol suggesting efflux by the multi-drug resistance pump. By comparing the uptake of Hoechst 33342 in the two cell lines that had been pretreated with hydroxytyrosol, it was determined that the polyphenol may have P-glycoprotein-modulating activity. Further, initial studies indicated modest radioprotective effects of relatively low doses of hydroxytyrosol in human keratinocytes. Analysis of mRNA sequencing data identified that treatment of keratinocytes with 20 μM hydroxytyrosol results in the upregulation of numerous antioxidant proteins and enzymes, including heme oxygenase-1 (15.46-fold upregulation), glutaredoxin (1.65) and glutathione peroxidase (1.53). This may account for the radioprotective activity of the compound, and reduction in oxidative stress suggests a mechanism for chemoprevention of cancer by hydroxytyrosol. Alteration in the expression of transcription factors may also contribute to the anti-cancer effects described in numerous studies. These include changes in the expression of STAT3, STAT6, SMAD7 and ETS-1. The telomerase subunit TERT was also found to be downregulated in K562 cells. Overall, our findings provide insights into the mechanisms of action of hydroxytyrosol, and more generally, we identify potential gene candidates for further exploration. Content Type Journal Article Category Research Paper Pages 1-13 DOI 10.1007/s12263-011-0249-3 Authors Haloom Rafehi, Epigenomic Medicine, Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, 75 Commercial Road, Melbourne, VIC, Australia Andrea J. Smith, Molecular Radiation Biology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia Aneta Balcerczyk, Epigenetics in Human Health and Disease, Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, VIC, Australia Mark Ziemann, Epigenetics in Human Health and Disease, Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, VIC, Australia Jenny Ooi, Epigenetics in Human Health and Disease, Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, VIC, Australia Shanon J. Loveridge, Epigenomic Medicine, Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, 75 Commercial Road, Melbourne, VIC, Australia Emma K. Baker, Epigenetics in Human Health and Disease, Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, VIC, Australia Assam El-Osta, Department of Pathology, The University of Melbourne, Parkville, VIC, Australia Tom C. Karagiannis, Epigenomic Medicine, Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, 75 Commercial Road, Melbourne, VIC, Australia Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description:    Changes in the inner mitochondrial membrane potential (∆ψ) may lead either to apoptosis or to protective autophagy. Connexin 43 (Cx43), a gap junction protein, is suggested to affect mitochondrial membrane permeability. The aim of our study was to analyze Cx43 gene expression, Cx43 protein localization and mitochondrial function in the human endothelial cells stressed by dietary-free fatty acids (FFA) and TNFα. Human endothelial cells (HUVECs) were incubated with (10–30 uM) palmitic (PA), oleic (OA), eicosapentaenoic (EPA) or arachidonic (AA) acids for 24 h. TNFα (5 ng/ml) was added at the last 4 h of incubation. The Cx43 gene expression was analyzed by the quantitative real-time PCR. The Cx43 protein concentrations in whole cells and in the isolated mitochondria were measured. Changes in ∆ψ and Cx43 localization were analyzed by flow cytometry or fluorescence microscopy. Generated ATP was measured by a luminescence assay. TNFα, PA and OA significantly decreased ∆ψ, while AA ( P  = 0.047) and EPA ( P  = 0.004) increased ∆ψ value. Preincubation with EPA or AA partially prevented the TNFα-induced decrease of ∆ψ. Incubation with AA resulted in up-regulation of the Cx43 gene expression. AA or PA significantly increased Cx43 protein content; however, presence of TNFα in general aggravated the negative effect of FFA. Only EPA was found to increase ATP generation in HUVECs. The fatty acid-specific induction of changes in Cx43 expression and protein concentration as well as the normalization of ∆ψ and increase of ATP generation seem to be the separate, independent mechanisms of FFA-mediated modulatory effect in the human endothelial cells pathology. Content Type Journal Article Category Research Paper Pages 1-7 DOI 10.1007/s12263-011-0247-5 Authors Beata Kiec-Wilk, Department of Clinical Biochemistry, Jagiellonian University Medical College, Krakow, Poland Urszula Czech, Department of Clinical Biochemistry, Jagiellonian University Medical College, Krakow, Poland Katarzyna Janczarska, Department of Clinical Biochemistry, Jagiellonian University Medical College, Krakow, Poland Anna Knapp, Department of Clinical Biochemistry, Jagiellonian University Medical College, Krakow, Poland Joanna Goralska, Department of Clinical Biochemistry, Jagiellonian University Medical College, Krakow, Poland Urszula Cialowicz, Department of Clinical Biochemistry, Jagiellonian University Medical College, Krakow, Poland Maciej T. Malecki, Department of Metabolic Diseases, Jagiellonian University Medical College, Kopernika 15 Str., 30-504, Krakow, Poland Aldona Dembinska-Kiec, Department of Clinical Biochemistry, Jagiellonian University Medical College, Krakow, Poland Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description:    Lipoprotein lipase (LPL) polymorphism correlated with LPL activity is associated with plasma lipid and lipoprotein levels. We aimed to investigate the frequency of LPL Pvu II polymorphism and effects of LPL Pvu II polymorphism and niacin intake on the prevalence of metabolic syndrome (MetSyn) in Koreans. Lifestyle questionnaires, anthropometry, and dietary records were completed, and LPL Pvu II polymorphism, LPL mass, and lipid profiles were determined in 548 Koreans (MetSyn: 278, Non-MetSyn: 270). The MetSyn group showed a significantly lower frequency of P1P1 (wild type) and a higher frequency of P1P2 (hetero type) than the non-MetSyn group. The P2P2 (mutant type) group significantly showed lower levels of HDLc and LPL mass and a higher level of TG than the P1P1 group. As niacin intake increased, LPL mass decreased in the P2P2 group ( r 2  = 0.07). In particular, the lowest niacin intake group (≤14.82 mg/day) increased more than 3 times with regard to a higher risk of MetSyn than the others in the P2P2 mutant groups. However, the MetSyn risk declined 74% at the optimal levels of niacin intake (14.83–17.80 mg/day) in the P2P2 group compared to those of the P1 allele group. The findings indicate that optimal levels of niacin intake effectively decreased Korean MetSyn prevalence in the P2P2 mutant group. Content Type Journal Article Category Research Paper Pages 1-11 DOI 10.1007/s12263-011-0251-9 Authors Eunjung Shin, Department of Food and Nutrition, Sungshin Women’s University, #249-1, 3-ga, Dongsun-dong, Sungbuk-ku, Seoul, 136-742 Korea Na-Young Park, Department of Food and Nutrition, Kyung Hee University, #1 Hoegi-dong, Dongdaemun-gu, Seoul, 130-701 Korea Yangsoo Jang, Division of Cardiology, Cardiovascular Genome Center, Yonsei University College of Medicine, Seoul, 120-752 Korea Hyunhee Oh, Department of Cellular and Molecular Physiology and Metabolism, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science, Incheon, 406-840 Korea Jayoung Jeong, Nutrition and Functional Food Research Division, Korea Food and Drug Administration, Cheongwon, Korea Yunsook Lim, Department of Food and Nutrition, Kyung Hee University, #1 Hoegi-dong, Dongdaemun-gu, Seoul, 130-701 Korea Myoungsook Lee, Department of Food and Nutrition, Sungshin Women’s University, #249-1, 3-ga, Dongsun-dong, Sungbuk-ku, Seoul, 136-742 Korea Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description:    Zinc (Zn) is an essential component of Zn-finger proteins and acts as a cofactor for enzymes required for cellular metabolism and in the maintenance of DNA integrity. The study investigated the genotoxic and cytotoxic effects of Zn deficiency or excess in a primary human oral keratinocyte cell line and determined the optimal concentration of two Zn compounds (Zn Sulphate (ZnSO 4 ) and Zn Carnosine (ZnC)) to minimise DNA damage. Zn-deficient medium (0 μM) was produced using Chelex treatment, and the two Zn compounds ZnSO 4 and ZnC were tested at concentrations of 0.0, 0.4, 4.0, 16.0, 32.0 and 100.0 μM. Cell viability was decreased in Zn-depleted cells (0 μM) as well as at 32 μM and 100 μM for both Zn compounds ( P  〈 0.0001) as measured via the MTT assay. DNA strand breaks, as measured by the comet assay, were found to be increased in Zn-depleted cells compared with the other treatment groups ( P  〈 0.05). The Cytokinesis Block Micronucleus Cytome assay showed a significant increase in the frequency of both apoptotic and necrotic cells under Zn-deficient conditions ( P  〈 0.05). Furthermore, elevated frequencies of micronuclei (MNi), nucleoplasmic bridges (NPBs) and nuclear buds (NBuds) were observed at 0 and 0.4 μM Zn, whereas these biomarkers were minimised for both Zn compounds at 4 and 16 μM Zn ( P  〈 0.05), suggesting these concentrations are optimal to maintain genome stability. Expression of PARP, p53 and OGG1 measured by western blotting was increased in Zn-depleted cells indicating that DNA repair mechanisms are activated. These results suggest that maintaining Zn concentrations within the range of 4–16 μM is essential for DNA damage prevention in cultured human oral keratinocytes. Content Type Journal Article Category Research Paper Pages 1-16 DOI 10.1007/s12263-011-0248-4 Authors Razinah Sharif, CSIRO Food and Nutritional Sciences, Adelaide, SA, Australia Philip Thomas, CSIRO Food and Nutritional Sciences, Adelaide, SA, Australia Peter Zalewski, School of Medicine, Faculty of Health Sciences, University of Adelaide, Adelaide, SA, Australia Michael Fenech, CSIRO Food and Nutritional Sciences, Adelaide, SA, Australia Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description:    Maternal nutrition during gestation influences the development of the fetus, thereby determining its phenotype, including nutrient metabolism, appetite, and feeding behavior. The control of appetite is a very complex process and can be modulated by orexigenic and anorexigenic mediators such as leptin, which is involved in the regulation of energy homeostasis by controlling food intake and energy expenditure. Leptin transcription and secretion are regulated by numerous factors, nutrition being one of them. The present study was designed to test whether maternal nutrition can permanently affect leptin gene transcription and leptin serum concentration in rat progeny. Moreover, we analyzed whether leptin expression and secretion in response to high-fat postweaning feeding depends on the maternal diet during gestation. Pregnant rats were fed either a normal protein, normal folic acid diet (the AIN-93 diet); a protein-restricted, normal folic acid diet; a protein-restricted, folic acid-supplemented diet; or a normal protein, folic acid-supplemented diet. After weaning, the progeny was fed either the AIN-93 diet or a high-fat diet. Neither maternal nutrition nor the postweaning diet significantly affected Lep transcription. High-fat feeding after weaning was associated with higher serum leptin concentration, but the reaction of an organism to the fat content of the diet was not determined by maternal nutrition during gestation. There was no correlation between Lep mRNA level and serum leptin concentration. Global DNA methylation in adipose tissue was about 30% higher in rats fed postnatally the high-fat diet ( P  〈 0.01). Our study showed that the protein and folic acid content in the maternal diet had no significant programming effect on Lep transcription and serum leptin concentration in the rats. Content Type Journal Article Category Research Paper Pages 1-6 DOI 10.1007/s12263-011-0239-5 Authors Agata Chmurzynska, Department of Human Nutrition and Hygiene, Poznań University of Life Sciences, Wojska Polskiego 31, 60-624 Poznań, Poland Monika Stachowiak, Department of Genetics and Animal Breeding, Poznań University of Life Sciences, Poznań, Poland Ewa Pruszynska-Oszmalek, Department of Animal Physiology and Biochemistry, Poznań University of Life Sciences, Poznań, Poland Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description:    The aim of the present work was to study the effects of benfotiamine (S-benzoylthiamine O-monophosphate) on glucose and lipid metabolism and gene expression in differentiated human skeletal muscle cells (myotubes) incubated for 4 days under normal (5.5 mM glucose) and hyperglycemic (20 mM glucose) conditions. Myotubes established from lean, healthy volunteers were treated with benfotiamine for 4 days. Glucose and lipid metabolism were studied with labeled precursors. Gene expression was measured using real-time polymerase chain reaction (qPCR) and microarray technology. Benfotiamine significantly increased glucose oxidation under normoglycemic (35 and 49% increase at 100 and 200 μM benfotiamine, respectively) as well as hyperglycemic conditions (70% increase at 200 μM benfotiamine). Benfotiamine also increased glucose uptake. In comparison, thiamine (200 μM) increased overall glucose metabolism but did not change glucose oxidation. In contrast to glucose, mitochondrial lipid oxidation and overall lipid metabolism were unchanged by benfotiamine. The expression of NADPH oxidase 4 (NOX4) was significantly downregulated by benfotiamine treatment under both normo- and hyperglycemic conditions. Gene set enrichment analysis (GSEA) showed that befotiamine increased peroxisomal lipid oxidation and organelle (mitochondrial) membrane function. In conclusion, benfotiamine increases mitochondrial glucose oxidation in myotubes and downregulates NOX4 expression. These findings may be of relevance to type 2 diabetes where reversal of reduced glucose oxidation and mitochondrial capacity is a desirable goal. Content Type Journal Article Category Research Paper Pages 1-11 DOI 10.1007/s12263-011-0252-8 Authors D. A. Fraser, Diabetes Research Centre, Oslo University Hospital, Oslo, Norway N. P. Hessvik, Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Oslo, Norway N. Nikolić, Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Oslo, Norway V. Aas, Faculty of Health Sciences, Oslo University College, Oslo, Norway K. F. Hanssen, Department of Endocrinology, Oslo University Hospital, Oslo, Norway S. K. Bøhn, Department of Nutrition, Faculty of Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway G. H. Thoresen, Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Oslo, Norway A. C. Rustan, Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Oslo, Norway Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description:    Signal transducers and activators of transcription (STAT) proteins were described as a family of latent cytosolic transcription factors whose activation is dependent on phosphorylation via growth factor- and cytokine-membrane receptors including interferon and interleukin, or by non-receptor intracellular tyrosine kinases, including Src. A vast majority of natural substances are capable of modulating mitogenic signals, cell survival, apoptosis, cell cycle regulation, angiogenesis as well as processes involved in metastasis development. The inhibition of STAT3 phosphorylation by natural and dietary compounds leads to decreased protein expression of STAT3 targets essentially involved in regulation of the cell cycle and apoptotic cell death. This review details the cell signaling pathways involving STAT transcription factors as well as the corresponding compounds from nature able to interfere with this regulatory system in human cancer. Content Type Journal Article Category Review Pages 1-15 DOI 10.1007/s12263-012-0281-y Authors Anne Trécul, Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Fondation de Recherche Cancer et Sang, Hôpital Kirchberg, 9 Rue Edward Steichen, 2540 Luxembourg, Luxembourg Franck Morceau, Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Fondation de Recherche Cancer et Sang, Hôpital Kirchberg, 9 Rue Edward Steichen, 2540 Luxembourg, Luxembourg Mario Dicato, Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Fondation de Recherche Cancer et Sang, Hôpital Kirchberg, 9 Rue Edward Steichen, 2540 Luxembourg, Luxembourg Marc Diederich, Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Fondation de Recherche Cancer et Sang, Hôpital Kirchberg, 9 Rue Edward Steichen, 2540 Luxembourg, Luxembourg Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description:    Protein acetylation status results from a balance between histone acetyltransferase and histone deacetylase (HDAC) activities. Alteration of this balance leads to a disruption of cellular integrity and participates in the development of numerous diseases, including cancer. Therefore, modulation of these activities appears to be a promising approach for anticancer therapy. Histone deacetylase inhibitors (HDACi) are epigenetically active drugs that induce the hyperacetylation of lysine residues within histone and non-histone proteins, thus affecting gene expression and cellular processes such as protein–protein interactions, protein stability, DNA binding and protein sub-cellular localization. Therefore, HDACi are promising anti-tumor agents as they may affect the cell cycle, inhibit proliferation, stimulate differentiation and induce apoptotic cell death. Over the last 30 years, numerous synthetic and natural products, including a broad range of dietary compounds, have been identified as HDACi. This review focuses on molecules from natural origins modulating HDAC activities and presenting promising anticancer activities. Content Type Journal Article Category Review Pages 1-11 DOI 10.1007/s12263-012-0283-9 Authors Carole Seidel, Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Fondation de Recherche Cancer et Sang, Hôpital Kirchberg, 9 Rue Edward Steichen, 2540 Luxembourg, Luxembourg Michael Schnekenburger, Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Fondation de Recherche Cancer et Sang, Hôpital Kirchberg, 9 Rue Edward Steichen, 2540 Luxembourg, Luxembourg Mario Dicato, Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Fondation de Recherche Cancer et Sang, Hôpital Kirchberg, 9 Rue Edward Steichen, 2540 Luxembourg, Luxembourg Marc Diederich, Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Fondation de Recherche Cancer et Sang, Hôpital Kirchberg, 9 Rue Edward Steichen, 2540 Luxembourg, Luxembourg Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description:    We examined the potential implication of skeletal muscle in the fat-lowering effect observed in mice treated with moderate doses of CLA. In experiment 1, mice fed with a standard-fat diet were orally treated with sunflower oil (control) and 3 or 10 mg CLA mixture/day for 37 days. In experiment 2, mice were fed with a high-fat diet for 65 days. For the first 30 days, they received the same doses as in experiment 1 and, from that time onwards, animals received double doses. Gene expression of key proteins involved in fatty acid transport, oxidation, regulation of lipid and carbohydrate utilization, composition of muscle fiber, and thermogenesis were determined and, in most of them, no major impact of CLA was seen. Therefore, enhancement of fatty acid oxidation in muscle did not seem to contribute to the antiobesity effect of CLA as seen in other studies with higher CLA doses. However, a strong induction of classically associated lipogenic genes such as Fasn (up to twofold) and, particularly, Scd1 (up to ninefold) was found. This activation could contribute to a protective role in muscle cells, since expression of ER stress markers was decreased and inversely correlated with the induction of Scd1. Content Type Journal Article Category Research Paper Pages 1-12 DOI 10.1007/s12263-011-0279-x Authors Pilar Parra, Laboratory of Molecular Biology, Nutrition and Biotechnology, University of the Balearic Islands and CIBER de Fisiopatología de la Obesidad y Nutrición (CIBER-OBN), Cra. Valldemossa Km 7.5, 07122 Palma de Mallorca, Spain Francisca Serra, Laboratory of Molecular Biology, Nutrition and Biotechnology, University of the Balearic Islands and CIBER de Fisiopatología de la Obesidad y Nutrición (CIBER-OBN), Cra. Valldemossa Km 7.5, 07122 Palma de Mallorca, Spain Andreu Palou, Laboratory of Molecular Biology, Nutrition and Biotechnology, University of the Balearic Islands and CIBER de Fisiopatología de la Obesidad y Nutrición (CIBER-OBN), Cra. Valldemossa Km 7.5, 07122 Palma de Mallorca, Spain Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description:    The most commonly used methods for assessing the selenium (Se) status in humans involve analysis of Se concentration, selenoprotein activity, and concentration in the blood and its compartments. Recently, it has been suggested that the expression of selenoprotein mRNA in circulating blood leukocytes could differently reflect Se status, due to prioritization of specific selenoprotein synthesis in response to dietary Se supply. Whereas the Se levels required for optimization of selenoprotein P level and plasma glutathione peroxidise activity are well known, estimation of Se level that is required for maximal mRNA expression of selenoprotein in humans is the subject of current investigations. Studies on rats suggest that whole blood selenoprotein mRNA level can be used as the relevant molecular biomarker for assessing Se status, and suboptimal Se intake may be sufficient to achieve effective expression. Human studies, however, did not confirm this hypothesis. According to studies on rodents and humans discussed in this review, it appears that suboptimal Se intake may be sufficient to satisfy molecular requirements of Se and it is lower than current recommended dietary intake in humans. The use of selenoprotein transcripts as a molecular biomarker of Se status requires further studies on a large group of healthy individuals with different baseline Se, including data regarding genetic polymorphism of selenoproteins and data regarding potential modifiers of Se metabolism. Content Type Journal Article Category Review Pages 1-11 DOI 10.1007/s12263-011-0246-6 Authors Edyta Reszka, Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, 8 Teresy St., 91-348 Lodz, Poland Ewa Jablonska, Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, 8 Teresy St., 91-348 Lodz, Poland Jolanta Gromadzinska, Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, 8 Teresy St., 91-348 Lodz, Poland Wojciech Wasowicz, Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, 8 Teresy St., 91-348 Lodz, Poland Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description:    Vitamin E (α-tocopherol) is a major lipid-soluble chain-breaking antioxidant in humans and mammals and plays an important role in normal development and physiology. The localization of α-tocopherol within the highly unsaturated phospholipid bilayer of cell membranes provides a means of controlling lipid oxidation at the initiation site. Mitochondria are the site for major oxidative processes and are important in fat oxidation and energy production, but a side effect is leakage of reactive oxygen species. Thus, incorporation of α-tocopherol and other antioxidants into mitochondria and other cellular compartments is important in order to maintain oxidative stability of the membrane-bound lipids and prevent damage from the reactive oxygen species. Many studies regarding mitochondrial disease and dysfunction have been performed in relation to deficiency of vitamin E and other antioxidants, whereas relatively sparse information is available regarding the eventual beneficial effects of antioxidant-enriched mitochondria in terms of health and function. This may be due to the fact that only little scientific information is available concerning the effect of supranutritional supplementation with antioxidants on their incorporation into mitochondria and other cellular membranes. The purpose of this review is therefore to briefly summarize experimental data performed with dietary vitamin E treatments in relation to the deposition of α-tocopherol in mitochondria and microsomes. Content Type Journal Article Category Review Pages 1-8 DOI 10.1007/s12263-012-0286-6 Authors Charlotte Lauridsen, Department of Animal Science, Faculty of Science and Technology, Aarhus University, P.O. Box 50, 8830 Tjele, Denmark Søren Krogh Jensen, Department of Animal Science, Faculty of Science and Technology, Aarhus University, P.O. Box 50, 8830 Tjele, Denmark Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description:    The innate immune receptor toll-like receptor 4 (TLR4) has been implicated in mediating some of the effects of dietary lipids on inflammation and type 2 diabetes (T2D). Similar to TLR4, the nucleotide-binding oligomerization domains (Nods) 1 and 2 are also proteins of innate immunity, which can respond to lipids and initiate pro-inflammatory signalling that plays a role in the aetiology of T2D. The objective was to determine the effect of Nod1 (Glu266Lys) and Nod2 (Ser268Pro) genotypes on factors associated with the metabolic syndrome (MetS), and whether they modify the association between dietary lipids and biomarkers of the MetS. Men and women ( n  = 998) between the ages of 20–29 years were genotyped for both polymorphisms, completed a one-month, semiquantitative food frequency questionnaire and provided a fasting blood sample. The Glu266Lys polymorphism in Nod1 was not associated with any of the biomarkers of the MetS, but modified the association between dietary saturated fat (SFA) and insulin sensitivity, as measured by HOMA-IR ( p for interaction = 0.04). Individuals with the Glu/Glu or Glu/Lys genotype showed no significant relationship between dietary SFA and HOMA-IR (β = −0.002 ± 0.006, p  = 0.77; and β = −0.003 ± 0.006, p  = 0.61), while those with the Lys/Lys genotype showed a positive association (β = 0.033 ± 0.02, p  = 0.03). The Nod2 Ser268Pro polymorphism was not associated with components of the MetS and did not modify the relationship between dietary lipid intake and the biomarkers of MetS. In summary, the Nod1 Glu266Lys polymorphism modifies the relationship between dietary SFA intake and HOMA-IR, suggesting that Nod1 may act as an intracellular lipid sensor affecting insulin sensitivity. Content Type Journal Article Category Research Paper Pages 1-9 DOI 10.1007/s12263-012-0287-5 Authors Cristina Cuda, Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, 150 College Street, Room 350, Toronto, ON M5S 3E2, Canada Alaa Badawi, Office of Biotechnology, Genomics and Population Health, Public Health Agency of Canada, Toronto, ON, Canada Mohamed Karmali, Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, 150 College Street, Room 350, Toronto, ON M5S 3E2, Canada Ahmed El-Sohemy, Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, 150 College Street, Room 350, Toronto, ON M5S 3E2, Canada Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description:    The apolipoprotein E (APOE) genotype is an important risk factor for ageing and age-related diseases. The APOE4 genotype (in contrast to APOE3) has been shown to be associated with oxidative stress and chronic inflammation. Metallothioneins (MT) exhibit antioxidant and anti-inflammatory activity, and MT overexpression has been shown to increase lifespan in mice. Interactions between APOE and MT, however, are largely unknown. Hence, we determined the effect of the APOE4 versus APOE3 genotype on MT levels in targeted gene replacement mice. APOE4 versus APOE3 mice exhibited significantly lower hepatic MT1 and MT2 mRNA as well as lower MT protein levels. The decrease in hepatic MT protein levels in APOE4 as compared to APOE3 mice was accompanied by lower nuclear Nrf1, a protein partly controlling MT gene expression. Cell culture experiments using hepatocytes identified allyl-isothiocyanate (AITC) as a potent MT inductor in vitro. Therefore, we supplemented APOE3 and APOE4 mice with AITC. However, AITC (15 mg/kg b.w.) could only partly correct for decreased MT1 and MT2 gene expression in APOE4 mice in vivo. Furthermore, cholesterol significantly decreased both Nrf1 and MT mRNA levels in Huh7 cells indicating that differences in MT gene expression between the two genotypes could be related to differences in hepatic cholesterol concentrations. Overall, present data suggest that the APOE genotype is an important determinant of tissue MT levels in mice and that MT gene expression may be impaired by the APOE4 genotype. Content Type Journal Article Category Research Paper Pages 1-9 DOI 10.1007/s12263-012-0282-x Authors Anne-Christin Graeser, Institute of Human Nutrition and Food Science, Christian-Albrechts-University Kiel, Hermann-Rodewald-Strasse 6, 24118 Kiel, Germany Patricia Huebbe, Institute of Human Nutrition and Food Science, Christian-Albrechts-University Kiel, Hermann-Rodewald-Strasse 6, 24118 Kiel, Germany Niels Storm, Bioglobe GmbH, Grandweg 64, 22529 Hamburg, Germany Wolfgang Höppner, Bioglobe GmbH, Grandweg 64, 22529 Hamburg, Germany Frank Döring, Institute of Human Nutrition and Food Science, Christian-Albrechts-University Kiel, Hermann-Rodewald-Strasse 6, 24118 Kiel, Germany Anika E. Wagner, Institute of Human Nutrition and Food Science, Christian-Albrechts-University Kiel, Hermann-Rodewald-Strasse 6, 24118 Kiel, Germany Gerald Rimbach, Institute of Human Nutrition and Food Science, Christian-Albrechts-University Kiel, Hermann-Rodewald-Strasse 6, 24118 Kiel, Germany Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description:    Although several epidemiological and intervention studies suggest that polyphenols (PPs) and PP-rich foods may improve memory and cognition in animals and humans, PPs’ mode of action is only poorly understood. To help distinguish between the different modes of action that have been proposed for PPs, it is obviously important to know how much PPs can accumulate in the brain, if any at all. However, reliable data on PP uptake into the brain of animals are limited as many studies failed to report important control procedures during data acquisition. In this paper, we summarize published data on the penetration of PPs into animal brain and review some hypotheses to explain the biological basis of potentially health-beneficial effects of PPs to the brain. Finally, we highlight promising new approaches, especially those of a hormetic dose-response and gut microbiota-brain interaction, which may allow a better understanding of PPs’ mode of action in animals and humans. Content Type Journal Article Category Review Pages 1-11 DOI 10.1007/s12263-011-0255-5 Authors Sebastian Schaffer, Department of Biochemistry, Centre for Life Sciences, National University of Singapore, 22 Medical Drive, Singapore, 117456 Singapore Barry Halliwell, Department of Biochemistry, Centre for Life Sciences, National University of Singapore, 22 Medical Drive, Singapore, 117456 Singapore Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description:    Due to protection of oncogenic proteins from degradation and enhancement of glycolytic phosphometabolites for synthetic processes, respectively, heat shock protein 90 (HSP90) and pyruvate kinase type M2 (PKM2) are important proteins for tumor growth. The present study was undertaken to investigate the susceptibility of both proteins and their encoding genes to the chemopreventive agent butyrate in human colon cells. Matched tissue of different transformation stages derived from 20 individual colon cancer patients was used for the experiments. The results of quantitative real-time PCR revealed a moderate increase of HSP90β and PKM2 mRNA in colon tumors ( P  〈 0.01) compared to normal tissues without relation to clinical parameters. The expression pattern could be confirmed for PKM2 protein by Western blot but not for HSP90β. During culturing with butyrate, the amount of PKM2 transcripts decreased in all three tissue types with the strongest effects observed in tumors (median fold decrease 45%, P  〈 0.05). The protein data have not reflected this influence supposing a more gradual degradation rate due to a longer half-life of PKM2. In contrast, the mRNA expression of HSP90β in normal tissue was found 1.38-fold increased by butyrate ( P  〈 0.05), but not the corresponding protein level. HSP90β expression in adenomas and tumors remained generally insensitive. Only in malignant tissue, however, a significant correlation was found between the individual effects observed on gene and protein expression level. In conclusion, the present study identified PKM2 as a potential direct target of butyrate in neoplastic colon tissue, whereas HSP90β is none of it. Content Type Journal Article Category Research Paper Pages 1-12 DOI 10.1007/s12263-011-0254-6 Authors Franziska Jahns, Department of Nutritional Toxicology, Institute of Nutrition, Friedrich-Schiller-University Jena, Jena, Germany Anne Wilhelm, Department of Nutritional Toxicology, Institute of Nutrition, Friedrich-Schiller-University Jena, Jena, Germany Karl Otto Greulich, Department of Single Cell and Single Molecule Techniques, Leibniz Institute of Age Research-Fritz Lipmann Institute, Jena, Germany Henning Mothes, Department of General, Visceral and Vascular Surgery, University Hospital, Friedrich-Schiller-University Jena, Jena, Germany Mariya Radeva, Department of Single Cell and Single Molecule Techniques, Leibniz Institute of Age Research-Fritz Lipmann Institute, Jena, Germany Anja Wölfert, Institute of Pathology, Friedrich-Schiller-University Jena, Jena, Germany Michael Glei, Department of Nutritional Toxicology, Institute of Nutrition, Friedrich-Schiller-University Jena, Jena, Germany Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description:    Exacerbated production of matrix metalloproteinases (MMPs) is a key event in the progression of osteoarthritis (OA) and represents a promising target for the management of OA with nutraceuticals. In this study, we sought to determine the MMP-inhibitory activity of an ethanolic Caesalpinia sappan extract (CSE) in human OA chondrocytes. Thus, human articular chondrocytes isolated from OA cartilage and SW1353 chondrocytes were stimulated with Interleukin-1beta (IL1β), without or with pretreatment with CSE. Following viability assays, the production of MMP-2 and MMP-13 was assessed using ELISA, whereas mRNA levels of MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-13 and TIMP-1, TIMP-2, TIMP-3 were quantified using RT-qPCR assays. Chondrocytes were co-transfected with a MMP-13 luciferase reporter construct and NF-kB p50 and p65 expression vectors in the presence or absence of CSE. In addition, the direct effect of CSE on the proteolytic activities of MMP-2 was evaluated using gelatin zymography. We found that CSE significantly suppressed IL1β-mediated upregulation of MMP-13 mRNA and protein levels via abrogation of the NF-kB(p65/p50)-driven MMP-13 promoter activation. We further observed that the levels of IL1β-induced MMP-1, MMP-3, MMP-7, and MMP-9 mRNA, but not TIMP mRNA levels, were down-regulated in chondrocytes in response to CSE. Zymographic results suggested that CSE did not directly interfere with the proteolytic activity of MMP-2. In summary, this study provides evidence for the MMP-inhibitory potential of CSE or CSE-derived compounds in human OA chondrocytes. The data indicate that the mechanism of this inhibition might, at least in part, involve targeting of NF-kB-mediated promoter activation. Content Type Journal Article Category Research Paper Pages 1-12 DOI 10.1007/s12263-011-0244-8 Authors Stefan Toegel, Department of Orthopaedics, Medical University Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria Shengqian Q. Wu, Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Vienna, Austria Miguel Otero, Laboratory of Cartilage Biology, Research Division, Hospital for Special Surgery, Weill Cornell Medical College, New York, NY, USA Mary B. Goldring, Laboratory of Cartilage Biology, Research Division, Hospital for Special Surgery, Weill Cornell Medical College, New York, NY, USA Pimporn Leelapornpisid, Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand Catharina Chiari, Department of Orthopaedics, Medical University Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria Alexander Kolb, Department of Orthopaedics, Medical University Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria Frank M. Unger, Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Vienna, Austria Reinhard Windhager, Department of Orthopaedics, Medical University Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria Helmut Viernstein, Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Vienna, Austria Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description:    The essential trace mineral selenium is an important determinant of oxidative stress susceptibility, with several studies showing an inverse relationship between selenium intake and cancer. Because different chemical forms of selenium have been reported to have varying bioactivity, there is a need for nutrigenomic studies that can comprehensively assess whether there are divergent effects at the molecular level. We examined the gene expression profiles associated with selenomethionine (SM), sodium selenite (SS), and yeast-derived selenium (YS) in the intestine, gastrocnemius, cerebral cortex, and liver of mice. Weanling mice were fed either a selenium-deficient (SD) diet (〈0.01 mg/kg diet) or a diet supplemented with one of three selenium sources (1 mg/kg diet, as either SM, SS or YS) for 100 days. All forms of selenium were equally effective in activating standard measures of selenium status, including tissue selenium levels, expression of genes encoding selenoproteins (Gpx1 and Txnrd2), and increasing GPX1 enzyme activity. However, gene expression profiling revealed that SS and YS were similar (and distinct from SM) in both the expression pattern of individual genes and gene functional categories. Furthermore, only YS significantly reduced the expression of Gadd45b in all four tissues and also reduced GADD45B protein levels in liver. Taken together, these results show that gene expression profiling is a powerful technique capable of elucidating differences in the bioactivity of different forms of selenium. Content Type Journal Article Category Research Paper Pages 1-11 DOI 10.1007/s12263-011-0243-9 Authors Jamie L. Barger, LifeGen Technologies, LLC, 510 Charmany Drive Suite 263, Madison, WI 53719, USA Tsuyoshi Kayo, LifeGen Technologies, LLC, 510 Charmany Drive Suite 263, Madison, WI 53719, USA Thomas D. Pugh, LifeGen Technologies, LLC, 510 Charmany Drive Suite 263, Madison, WI 53719, USA James A. Vann, LifeGen Technologies, LLC, 510 Charmany Drive Suite 263, Madison, WI 53719, USA Ronan Power, Alltech Biotechnology, Nicholasville, KY, USA Karl Dawson, Alltech Biotechnology, Nicholasville, KY, USA Richard Weindruch, Department of Medicine and Veterans Administration Hospital, University of Wisconsin-Madison, Madison, WI, USA Tomas A. Prolla, Departments of Genetics and Medical Genetics, University of Wisconsin, Madison, WI, USA Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description:    Ginsenosides, bioactive compounds of Panax Ginseng C.A. Meyer , are divided into protopanaxadiol (PD) and protopanaxtriol (PT). The aim of this study was to evaluate the protective effects of different PD and PT combination ratios on liver inflammation and apoptosis in hyperlipidemic apo E KO mice. R1 (PD/PT = 1, high Rg 1 and Rb 1 ) and R2 (PD/PT = 2, high Re and Rd) extracts were intraperitoneally injected by 100 mg/kg/day at the 8th week. R1 and R2 improved atherogenic indices by increasing HDL and lowering total cholesterol (TC) and triacylglyceride (TG) selectively. R1 decreased lipid peroxides (LPO) level in plasma and liver tissue of hyperlipidemic mice, and R2 lowered plasma malondialdehyde(MDA) level. R1 and R2 not only regulated the expression of cyclooxygenase (COX)-2, IκB-α, phopho-ERK 1/2, and phopho-SAPK/JNK levels but also were significantly effective in blocking apoptotic signals, such as caspase-8, -9, as well as the cleavage of PARP in liver. Different combinational treatment of PD and PT extracts might ameliorate the liver inflammation and apoptosis in hyperlipidemic apo E KO mice, which is atherosclerotic animal model. Content Type Journal Article Category Research Paper Pages 1-11 DOI 10.1007/s12263-011-0245-7 Authors Soojeong Jang, Department of Food and Nutrition, Nutrition Biochem Lab, Sungshin Women’s University, #249-1, 3-ga, Dongsun-dong, Sungbuk-ku, Seoul, 136-742 Republic of Korea Yunsook Lim, Department of Food and Nutrition, Kyung Hee University, #1 Hoegi-dong, Dongdaemun-gu, Seoul, 130-701 Republic of Korea Giuseppe Valacchi, Department of Food and Nutrition, Kyung Hee University, #1 Hoegi-dong, Dongdaemun-gu, Seoul, 130-701 Republic of Korea Sungbin Sorn, Department of Biological Sciences, College of Life Science and Bioengineering, Korea Advanced Institute of Science and Technology, Daejeon city, Republic of Korea Hyon Park, Department of Sport Medicine, College of Physical Education, Kyung Hee University, Yongin, Republic of Korea Na-Young Park, Department of Food and Nutrition, Kyung Hee University, #1 Hoegi-dong, Dongdaemun-gu, Seoul, 130-701 Republic of Korea Myoungsook Lee, Department of Food and Nutrition, Nutrition Biochem Lab, Sungshin Women’s University, #249-1, 3-ga, Dongsun-dong, Sungbuk-ku, Seoul, 136-742 Republic of Korea Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description:    Conjugated linoleic acids (CLAs) are natural PPARγ ligands, which showed conflicting effects on metabolism in humans. We examined metabolic effects of different isomers of CLA in subjects with PPARγ2 Pro12Ala polymorphisms. A total of 35 men underwent four intervention periods in a crossover study design: subjects with either genotypes received c9, t11 CLA or t10, c12 CLA, a commercially available 1:1 mix of both isomers or reference oil (linoleic acid (LA)). Adipocytokines, insulin, glucose and triglycerides were assessed in the fasting state and after a standardized mixed meal. Across all genotypes, there was a significant ( p  = 0.025) CLA treatment effect upon postprandial (pp) HOMA-IR values, with c9, t11 CLA and CLA isomer mix improving, but t10, c12 CLA isomer worsening. In Ala12Ala subjects, the t10, c12 isomer caused weight gain ( p  = 0.03) and tended to increase postprandial insulin levels ( p  = 0.05). In Pro12Pro subjects, t10, c12 resulted in reduction in waist circumference ( p  = 0.03). The comparison of the different genotype groups revealed statistically different changes in fasting and postprandial insulin, HOMA-IR and leptin after intervention. c9, t11 CLA and the commercial CLA mix showed beneficial effects on insulin sensitivity compared with LA, while t10, c12 CLA adversely affects body weight and insulin sensitivity in different PPAR genotypes. CLA isomers have different effects on metabolism in Ala and Pro carriers. Content Type Journal Article Category Research Paper Pages 1-11 DOI 10.1007/s12263-012-0289-3 Authors Diana Rubin, Department of Physiology and Biochemistry of Nutrition, Max Rubner Institute, Kiel, Germany Julia Herrmann, Department of Physiology and Biochemistry of Nutrition, Max Rubner Institute, Kiel, Germany Daniela Much, Division of Metabolic and Nutritional Medicine, Dr. von Hauner Children’s Hospital, University of Munich Medical Centre, Munich, Germany Maria Pfeuffer, Department of Physiology and Biochemistry of Nutrition, Max Rubner Institute, Kiel, Germany C. Laue, Center of Clinical Research, Tecura GmbH, Kiel, Germany P. Winkler, Center of Clinical Research, Tecura GmbH, Kiel, Germany Ulf Helwig, Department of Physiology and Biochemistry of Nutrition, Max Rubner Institute, Kiel, Germany Doris Bell, Project Management Agency at German Aerospace Center, Heinrich-Koenen-Str.1, 53227 Bonn, Germany Annegret Auinger, Department of Physiology and Biochemistry of Nutrition, Max Rubner Institute, Kiel, Germany Stephanie Darabaneanu, Institute of Medical Psychology, University Clinic of Kiel, Kiel, Germany Andreas Ruether, Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany Jürgen Schrezenmeir, Department of Physiology and Biochemistry of Nutrition, Max Rubner Institute, Kiel, Germany Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description:    Evidence of enhanced oxidative stress (O.S.) and lipid peroxidation has been reported in patients with Rett syndrome (RTT), a relatively rare neurodevelopmental disorder progressing in 4-stages, and mainly caused by loss-of-function mutations in the methyl-CpG-binding protein 2. No effective therapy for preventing or arresting the neurologic regression in the disease in its various clinical presentations is available. Based on our prior evidence of enhanced O.S. and lipid peroxidation in RTT patients, herein we tested the possible therapeutic effects of ω-3 polyunsaturated fatty acids (ω-3 PUFAs), known antioxidants with multiple effects, on the clinical symptoms and O.S. biomarkers in the earliest stage of RTT. A total of 20 patients in stage I were randomized ( n  = 10 subjects per arm) to either oral supplementation with ω-3 PUFAs-containing fish oil (DHA: 72.9 ± 8.1 mg/kg b.w./day; EPA: 117.1 ± 13.1 mg/kg b.w./day; total ω-3 PUFAs: 246.0 ± 27.5 mg/kg b.w./day) for 6 months or no treatment. Primary outcomes were potential changes in clinical symptoms, with secondary outcomes including variations for five O.S. markers in plasma and/or erythrocytes (nonprotein bound iron, F 2 -dihomo-isoprostanes, F 3 -isoprostanes, F 4 -neuroprostanes, and F 2 -isoprostanes). A significant reduction in the clinical severity (in particular, motor-related signs, nonverbal communication deficits, and breathing abnormalities) together with a significant decrease in all the examined O.S. markers was observed in the ω-3 PUFAs supplemented patients, whereas no significant changes were evidenced in the untreated group. For the first time, these findings strongly suggest that a dietary intervention in this genetic disease at an early stage of its natural history can lead to a partial clinical and biochemical rescue. Content Type Journal Article Category Research Paper Pages 1-12 DOI 10.1007/s12263-012-0285-7 Authors Claudio De Felice, Neonatal Intensive Care Unit, University Hospital Azienda Ospedaliera Universitaria Senese (AOUS) of Siena, S. M. Le Scotte General Hospital, Viale M. Bracci, 16, 53100 Siena, Italy Cinzia Signorini, Department of Pathophysiology, Experimental Medicine and Public Health, University of Siena, Siena, Italy Thierry Durand, Institut des Biomolécules Max Mousseron (IBMM), UMR 5247 CNRS, UM I, UM II, Montpellier, France Lucia Ciccoli, Department of Pathophysiology, Experimental Medicine and Public Health, University of Siena, Siena, Italy Silvia Leoncini, Department of Pathophysiology, Experimental Medicine and Public Health, University of Siena, Siena, Italy Maurizio D’Esposito, Institute of Genetics and Biophysics “Adriano Buzzati Traverso” CNR, Napoli, Italy Stefania Filosa, Institute of Genetics and Biophysics “Adriano Buzzati Traverso” CNR, Napoli, Italy Camille Oger, Institut des Biomolécules Max Mousseron (IBMM), UMR 5247 CNRS, UM I, UM II, Montpellier, France Alexandre Guy, Institut des Biomolécules Max Mousseron (IBMM), UMR 5247 CNRS, UM I, UM II, Montpellier, France Valérie Bultel-Poncé, Institut des Biomolécules Max Mousseron (IBMM), UMR 5247 CNRS, UM I, UM II, Montpellier, France Jean-Marie Galano, Institut des Biomolécules Max Mousseron (IBMM), UMR 5247 CNRS, UM I, UM II, Montpellier, France Alessandra Pecorelli, Department of Pathophysiology, Experimental Medicine and Public Health, University of Siena, Siena, Italy Laura De Felice, Multimedia Content Design Master Course, University of Florence, Florence, Italy Giuseppe Valacchi, Department of Evolutionary Biology, University of Ferrara, Ferrara, Italy Joussef Hayek, Child Neuropsychiatry Unit, University Hospital, AOUS, Siena, Italy Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description:    Genomics-based technologies produce large amounts of data. To interpret the results and identify the most important variates related to phenotypes of interest, various multivariate regression and variate selection methods are used. Although inspected for statistical performance, the relevance of multivariate models in interpreting biological data sets often remains elusive. We compare various multivariate regression and variate selection methods applied to a nutrigenomics data set in terms of performance, utility and biological interpretability. The studied data set comprised hepatic transcriptome (10,072 predictor variates) and plasma protein concentrations [2 dependent variates: Leptin (LEP) and Tissue inhibitor of metalloproteinase 1 (TIMP-1)] collected during a high-fat diet study in ApoE3Leiden mice. The multivariate regression methods used were: partial least squares “PLS”; a genetic algorithm-based multiple linear regression, “GA-MLR”; two least-angle shrinkage methods, “LASSO” and “ELASTIC NET”; and a variant of PLS that uses covariance-based variate selection, “CovProc.” Two methods of ranking the genes for Gene Set Enrichment Analysis (GSEA) were also investigated: either by their correlation with the protein data or by the stability of the PLS regression coefficients. The regression methods performed similarly, with CovProc and GA performing the best and worst, respectively ( R -squared values based on “double cross-validation” predictions of 0.762 and 0.451 for LEP; and 0.701 and 0.482 for TIMP-1). CovProc, LASSO and ELASTIC NET all produced parsimonious regression models and consistently identified small subsets of variates, with high commonality between the methods. Comparison of the gene ranking approaches found a high degree of agreement, with PLS-based ranking finding fewer significant gene sets. We recommend the use of CovProc for variate selection, in tandem with univariate methods, and the use of correlation-based ranking for GSEA-like pathway analysis methods. Content Type Journal Article Category Research Paper Pages 1-11 DOI 10.1007/s12263-012-0288-4 Authors Henri S. Tapp, Institute of Food Research, Norwich Research Park, Colney Lane, Norwich, NR4 7UA UK Marijana Radonjic, TNO, Microbiology and Systems Biology, P.O. Box 360, 3700 AJ Zeist, The Netherlands E. Kate Kemsley, Institute of Food Research, Norwich Research Park, Colney Lane, Norwich, NR4 7UA UK Uwe Thissen, Nutrigenomics Consortium, Top Institute Food and Nutrition, P.O. Box 557, 6700 AN Wageningen, The Netherlands Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description:    Personal genetic information has become increasingly accessible to the public as a result of direct-to-consumer (DTC) genetic tests; however, concerns have been raised over their value and potential risks. We compared the effects of providing genotype-based dietary advice with general recommendations on behavioral outcomes using a randomized controlled study. Participants were men and women from the Toronto Nutrigenomics and Health Study between the ages of 20–35 years ( n  = 149) who completed a survey to assess their awareness of DTC genetic tests and nutrigenomics, as well as potential motivations for undergoing genetic testing. Participants were then randomized into an intervention (I) or control (C) group and were given either genotype-based personalized dietary advice or general dietary advice, respectively. A second survey was administered to assess the participants’ opinions of the dietary reports they received. A greater proportion of participants in the intervention group agreed that they understood the dietary advice they were given (93% (I) vs. 78% (C); p  = 0.009). Participants in the intervention group were more likely to agree that the dietary recommendations they received would be useful when considering their diet (88% (I) vs. 72% (C); p  = 0.02) and wanted to know more about the recommendations (95% (I) vs. 76% (C); p  〈 0.0001). Only 9% of participants in the intervention group reported feeling uneasy about learning their genetic information. These findings suggest that individuals find dietary recommendations based on genetics more understandable and more useful than general dietary advice. Very few feel uneasy about receiving their genetic information that relates to personalized nutrition. Content Type Journal Article Category Research Paper Pages 1-8 DOI 10.1007/s12263-012-0290-x Authors Daiva E. Nielsen, Department of Nutritional Sciences, Room 350, University of Toronto, 150 College St, Toronto, ON M5S 3E2, Canada Ahmed El-Sohemy, Department of Nutritional Sciences, Room 350, University of Toronto, 150 College St, Toronto, ON M5S 3E2, Canada Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description:    Copper deficiency leads to anemia but the mechanism is unknown. Copper deficiency also leads to hypoferremia, which may limit erythropoiesis. The hypoferremia may be due to limited function of multicopper oxidases (MCO) hephaestin in enterocytes or GPI-ceruloplasmin in macrophages of liver and spleen whose function as a ferroxidase is thought essential for iron transfer out of cells. Iron release may also be limited by ferroportin (Fpn), the iron efflux transporter. Fpn may be lower following copper deficiency because of impaired ferroxidase activity of MCO. Fpn is also dependent on the liver hormone hepcidin as Fpn is degraded when hepcidin binds to Fpn. Anemia and hypoferremia both down regulate hepcidin by separate mechanisms. Current studies confirmed and extended earlier studies with copper-deficient (CuD) rats that suggested low hepicidin resulted in augmented Fpn. However, current studies in CuD dams failed to confirm a correlation that hepcidin expression was associated with low transferrin receptor 2 (TfR2) levels and also challenged the dogma that holotransferrin can explain the correlation with hepcidin. CuD dams exhibited hypoferremia, low liver TfR2, anemia in some rats, yet no depression in Hamp expression , the hepcidin gene. Normal levels of GDF-15, the putative erythroid cytokine that suppresses hepcidin, were detected in plasma of CuD and iron-deficient (FeD) dams. Importantly, FeD dams did display greatly lower Hamp expression. Normal hepcidin in these CuD dams is puzzling since these rats may need extra iron to meet needs of lactation and the impaired iron transfer noted previously. Content Type Journal Article Category Research Paper Pages 1-10 DOI 10.1007/s12263-012-0293-7 Authors Margaret Broderius, Department of Biomedical Sciences, University of Minnesota Medical School Duluth, 1035 University Drive, Duluth, MN 55812, USA Elise Mostad, Department of Biomedical Sciences, University of Minnesota Medical School Duluth, 1035 University Drive, Duluth, MN 55812, USA Joseph R. Prohaska, Department of Biomedical Sciences, University of Minnesota Medical School Duluth, 1035 University Drive, Duluth, MN 55812, USA Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description:    Hydrogen sulphide (H 2 S) is a gaseous signalling molecule that regulates blood flow and pressure. It is synthesised from cysteine via cystathionine β-synthase and cystathionine γ-lyase. We examined whether thiol precursors of H 2 S, transsulphuration pathway gene variants (CBS-844ins68 and CTH-G1364T) and key B-vitamin cofactors might be critical determinants of hypertension in an elderly Australian population. An elderly Australian retirement village population ( n  = 228; age 65–96 years, 91 males and 137 females) was assessed for the prevalence of two transsulphuration pathway–related variant genes associated with cysteine synthesis and hence H 2 S production. Thiols were determined by HPLC, genotypes by PCR and dietary intake by food frequency questionnaire. Homocysteine levels were statistically higher in the hypertensive phenotype ( p  = 0.0399), but there was no difference for cysteine or glutathione. Using nominal logistic regression, cysteine, CTH-G1364T genotype, dietary synthetic folate and vitamin B 6 predicted clinical phenotype (determined as above/below 140/90 mm Hg) and then only in female subjects ( p  = 0.0239, 0.0178, 0.0249 and 0.0371, respectively). Least-squares regression supports cysteine being highly inversely predictive of diastolic blood pressure: p and r 2 values 〈0.0001 and 0.082; 0.0409 and 0.046; and 〈0.0001 and 0.113 for all subjects, males and females, respectively. Additionally, CTH-G1364T genotype predicts diastolic blood pressure in males ( p  = 0.0217; r 2  = 0.083), but contrasts with observations for females. Overall, analyses, including stepwise regression, suggest cysteine, dietary natural and synthetic folate, vitamins B 6 and B 12 , and both genetic variants (CTH-C1364T and CBS-844ins68) are all aetiologically relevant in the regulation of blood pressure. Hydrogen sulphide is a vasorelaxant gasotransmitter with characteristics similar to nitric oxide. Cysteine and the G1364T and 844ins68 variants of the cystathionine γ-lyase and cystathionine β-synthase genes, respectively, are the biological determinants of H 2 S synthesis, and all three are shown here to influence the hypertensive phenotype. Additionally, B-vitamin cofactors for these three enzymes may also be important determinants of blood pressure. Content Type Journal Article Category Research Paper Pages 1-9 DOI 10.1007/s12263-012-0317-3 Authors Mark Lucock, School of Environmental and Life Sciences, University of Newcastle, PO Box 127, Brush Rd, Ourimbah, NSW 2258, Australia Zoë Yates, School of Environmental and Life Sciences, University of Newcastle, PO Box 127, Brush Rd, Ourimbah, NSW 2258, Australia Charlotte Martin, School of Environmental and Life Sciences, University of Newcastle, PO Box 127, Brush Rd, Ourimbah, NSW 2258, Australia Jeong-Hwa Choi, School of Environmental and Life Sciences, University of Newcastle, PO Box 127, Brush Rd, Ourimbah, NSW 2258, Australia Lyndell Boyd, School of Environmental and Life Sciences, University of Newcastle, PO Box 127, Brush Rd, Ourimbah, NSW 2258, Australia Sa Tang, School of Environmental and Life Sciences, University of Newcastle, PO Box 127, Brush Rd, Ourimbah, NSW 2258, Australia Nenad Naumovski, School of Environmental and Life Sciences, University of Newcastle, PO Box 127, Brush Rd, Ourimbah, NSW 2258, Australia Paul Roach, School of Environmental and Life Sciences, University of Newcastle, PO Box 127, Brush Rd, Ourimbah, NSW 2258, Australia Martin Veysey, Teaching and Research Unit, Central Coast Local Health District, PO Box 361, Gosford, NSW 2250, Australia Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description:    A high-fat diet (HFD) has been recognized as a risk factor for diseases such as dyslipidemia, atherosclerosis, obesity, and osteoporosis. However, studies analyzing gene expression after HFD in bone are rare. That prompted us to analyze the expression of selected genes in bone of 4-week-old diabetes-prone B(io)B(reeding) rats. Two breeding pairs were fed a HFD (+10 % tallow) or were fed a normal diet (ND; Ssniff R-Z) before mating and afterward during pregnancy. After the birth of progeny, parents continued to be given HFD or ND until the progeny was weaned (3 weeks). Thereafter, offspring were weaned and were fed the same food as their parents up to an age of 4 weeks. Body weight was measured at an age of 4 weeks, and subsequently 13 HFD rats and 13 ND rats were killed and the tibial bone was harvested to analyze the expression of 53 genes in bone. All rats fed HFD were significantly heavier than rats fed ND after 3 and 4 weeks. The diet also influenced the expression of genes in bone. There were significant differences in 20 out of 53 genes studied between rats fed HFD compared with rats fed ND. Four out of 20 had a lower and 17 out of 20 genes a higher expression in HFD rats, but differences in gene expression showed obvious differences between males and females. There were only two genes that were similarly different between males and females: Bmp4 and Atf4. Two genes, Foxg1 and Npy , were inversely expressed in males and females. It seems that the gene expression is differently regulated by diet during pregnancy and later in life between males and females. Nevertheless, it cannot be excluded that HFD also acts as an epigenetic factor in the development of offspring in utero. Content Type Journal Article Category Research Paper Pages 1-6 DOI 10.1007/s12263-012-0299-1 Authors Jörn Lange, Department of Trauma and Reconstructive Surgery, Medical Faculty, University of Greifswald, Greifswald, Germany Thomas Barz, Department of Orthopaedic Surgery, Asklepios Klinikum Uckermark, Schwedt, Germany Axel Ekkernkamp, Department of Trauma and Reconstructive Surgery, Medical Faculty, University of Greifswald, Greifswald, Germany Ingrid Klöting, Department of Laboratory Animal Science, Medical Faculty, University of Greifswald, 17495 Karlsburg, Greifswald, Germany Niels Follak, Orthopedic Clinic, Pfeiffersche Stiftungen, Magdeburg, Germany Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description:    Breast cancer is the leading cause of cancer deaths in women. Diet and lifestyle are major contributing factors to increased breast cancer risk. While mechanisms underlying dietary protection of mammary tumor formation are increasingly elucidated, there remains a dearth of knowledge on the nature and precise actions of specific bioactive components present in foods with purported health effects. The 43-amino acid peptide lunasin (LUN) is found in soybeans, is bioavailable similar to the isoflavone genistein (GEN), and thus may mediate the beneficial effects of soy food consumption. Here, we evaluated whether LUN displays common and distinct actions from those of GEN in non-malignant (mouse HC11) and malignant (human MCF-7) mammary epithelial cells. In MCF-7 cells, LUN up-regulated tumor suppressor phosphatase and tensin homolog deleted in chromosome ten (PTEN) promoter activity, increased PTEN transcript and protein levels and enhanced nuclear PTEN localization, similar to that shown for GEN in mammary epithelial cells. LUN-induced cellular apoptosis, akin to GEN, was mediated by PTEN, but unlike that for GEN, was p53-independent. LUN promoted E-cadherin and β-catenin non-nuclear localization similar to GEN, but unlike GEN, did not influence the proliferative effects of oncogene Wnt1 on HC11 cells. Further, LUN did not recapitulate GEN inhibitory effects on expansion of the cancer stem-like/progenitor population in MCF-7 cells. Results suggest the concerted actions of GEN and LUN on cellular apoptosis for potential mammary tumor preventive effects and highlight whole food consumption rather than intake of specific dietary supplements with limited biological effects for greater health benefits. Content Type Journal Article Category Research Paper Pages 1-12 DOI 10.1007/s12263-012-0307-5 Authors John Mark P. Pabona, Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA Bhuvanesh Dave, Arkansas Children’s Nutrition Center, 15 Children’s Way, Little Rock, AR 72202, USA Ying Su, Arkansas Children’s Nutrition Center, 15 Children’s Way, Little Rock, AR 72202, USA Maria Theresa E. Montales, Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA Ben O. de Lumen, University of California Berkeley, Berkeley, CA 94720, USA Elvira G. de Mejia, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA Omar M. Rahal, Arkansas Children’s Nutrition Center, 15 Children’s Way, Little Rock, AR 72202, USA Rosalia C. M. Simmen, Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description:    Genome-wide association studies (GWASs) have become a very important tool to address the genetic origin of phenotypic variability, in particular associated with diseases. Nevertheless, these types of studies provide limited information about disease etiology and the molecular mechanisms involved. Recently, the incorporation of metabolomics into the analysis has offered novel opportunities for a better understanding of disease-related metabolic deregulation. The pattern emerging from this work is that gene-driven changes in metabolism are prevalent and that common genetic variations can have a profound impact on the homeostatic concentrations of specific metabolites. A particularly interesting aspect of this work takes into account interactions of environment and lifestyle with the genome and how this interaction translates into changes in the metabolome. For instance, the role of PYROXD2 in trimethylamine metabolism points to an interaction between host and microbiome genomes (host/microbiota). Often, these findings reveal metabolic deregulations, which could eventually be tuned with a nutritional intervention. Here we review the development of gene–metabolism association studies from a single-gene/single-metabolite to a genome-wide/metabolome-wide approach and highlight the conceptual changes associated with this ongoing transition. Moreover, we report some of our recent GWAS results on a cohort of 265 individuals from an ethnically diverse population that validate and refine previous findings on gene–urine metabolism interactions. Specifically, our results confirm the effect of PYROXD2 polymorphisms on trimethylamine metabolism and suggest that a previously reported association of N -acetylated compounds with the ALMS1/NAT8 locus is driven by SNPs in the ALMS1 gene. Content Type Journal Article Category Review Pages 1-9 DOI 10.1007/s12263-012-0313-7 Authors Ivan Montoliu, Nestlé Research Center, Bioanalytical Science, Nestec Ltd., 1000 Lausanne 26, Switzerland Ulrich Genick, Nestlé Research Center, Perception Physiology, Nestec Ltd., 1000 Lausanne 26, Switzerland Mirko Ledda, Nestlé Research Center, Perception Physiology, Nestec Ltd., 1000 Lausanne 26, Switzerland Sebastiano Collino, Nestlé Research Center, Bioanalytical Science, Nestec Ltd., 1000 Lausanne 26, Switzerland François-Pierre Martin, Nestlé Research Center, Bioanalytical Science, Nestec Ltd., 1000 Lausanne 26, Switzerland Johannes le Coutre, Nestlé Research Center, Perception Physiology, Nestec Ltd., 1000 Lausanne 26, Switzerland Serge Rezzi, Nestlé Research Center, Bioanalytical Science, Nestec Ltd., 1000 Lausanne 26, Switzerland Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description:    The relationship between genetic and the environment represents a pathway to better understand individual variations in nutrition intake and food preferences. However, the present literature is weakened somewhat by methodological flaws (e.g., overreliance on self-report questionnaires), discrepancies in statistical approaches, and inconsistent findings. Little research on this topic to date has included examination of micronutrient intake. The purpose of this study is to improve the existing literature on genetic and environmental influences on energy and nutrient intake by addressing these gaps. Twin pairs ( N  = 358; age 11–13 years) provided 3-day food intake diaries, which were assessed for intake of total energy, macronutrients, and micronutrients. Structural equation modeling revealed that genetic influences accounted for a significant portion of the total variance in total energy (48 %), macronutrients (35–45 %), minerals (45 %), and vitamins (21 %). Consistent with previous studies, the shared environment appeared to contribute little to nutritional intake. Findings on vitamin and mineral intake are novel and are particularly beneficial for further research on the contribution of micronutrients to individual physical health status. Better understanding of the linkage between genes, environment, and nutritional intake and deficiencies can clarify behavioral and physical outcomes, potentially informing risk reduction, primary prevention, and intervention strategies. Content Type Journal Article Category Research Paper Pages 1-12 DOI 10.1007/s12263-012-0320-8 Authors Jianghong Liu, Faculty, School of Nursing and School of Medicine, University of Pennsylvania, 418 Curie Blvd., Room 426, Claire M. Fagin Hall, Philadelphia, PA 19104-6096, USA Catherine Tuvblad, Department of Psychology, University of Southern California, Los Angeles, CA, USA Adrian Raine, Departments of Criminology, Psychiatry, and Psychology, University of Pennsylvania, Philadelphia, PA, USA Laura Baker, Department of Psychology, University of Southern California, Los Angeles, CA, USA Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description:    The detrimental effects of high oxygen supplementation have been widely reported. Conversely, few is known about the effects of exposure to mild hyperoxic conditions, an interesting issue since the use of oxygen-enriched mixture is now increasingly used in clinical practice and especially for professional and recreational reasons. Our study investigated if in vitro exposure of human umbilical vein endothelial cells (HUVECs) to moderate hyperoxia (O 2 32 %) induces cellular alterations, measured as changes in cell signaling pathways. Furthermore, by means of an ex vivo experimental model where human volunteers were used as bioreactors, we studied whether anthocyanin metabolites are able to protect HUVECs against mild hyperoxia-induced damage. We observed that the cytotoxic effect of mild hyperoxia came along with a significant decrease in nuclear accumulation of the transcription factor Nrf2, as well as in the expression of Nrf2-regulated antioxidant and cytoprotective genes. Furthermore, under normoxic conditions, anthocyanin metabolites appeared able to activate the Nrf2 pathway, through the involvement of specific kinases (ERK1/2); this adaptive effect may explain the protective effect observed in mild hyperoxia-exposed HUVECs following anthocyanin pretreatment. This study confirms that dietary anthocyanins and/or their metabolites can protect endothelial cells against mild hyperoxia-induced alterations acting as cell signaling modulators. Content Type Journal Article Category Research Paper Pages 1-9 DOI 10.1007/s12263-012-0324-4 Authors Francesco Cimino, Department Farmaco-Biologico, University of Messina, Viale Annunziata, 98168 Messina, Italy Antonio Speciale, Department Farmaco-Biologico, University of Messina, Viale Annunziata, 98168 Messina, Italy Sirajudheen Anwar, Department Farmaco-Biologico, University of Messina, Viale Annunziata, 98168 Messina, Italy Raffaella Canali, National Research Institute for Food and Nutrition, Via Ardeatina 546, 00178 Rome, Italy Elisabetta Ricciardi, Department Farmaco-Biologico, University of Messina, Viale Annunziata, 98168 Messina, Italy Fabio Virgili, National Research Institute for Food and Nutrition, Via Ardeatina 546, 00178 Rome, Italy Domenico Trombetta, Department Farmaco-Biologico, University of Messina, Viale Annunziata, 98168 Messina, Italy Antonina Saija, Department Farmaco-Biologico, University of Messina, Viale Annunziata, 98168 Messina, Italy Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description:    Monounsaturated fatty acids (MUFA) have been viewed as either beneficial or neutral with respect to health; however, recent evidence suggests that MUFA may be associated with obesity and cardiovascular disease. Sex differences in MUFA composition have been reported in both rats and humans, but the basis for this sexual dimorphism is unknown. In the current study, enzymes involved in MUFA biosynthesis are examined in rat and cell culture models. Male and female rats were maintained on an AIN-93G diet prior to killing at 14 weeks of age after an overnight fast. Concentrations of 16:0 (2,757 ± 616 vs. 3,515 ± 196 μg fatty acid/g liver in males), 18:1n-7 (293 ± 66 vs. 527 ± 49 μg/g) and 18:1n-9 (390 ± 80 vs. 546 ± 47 μg/g) were lower, and concentrations of 18:0 (5,943 ± 1,429 vs. 3,987 ± 325 μg/g) were higher in phospholipids in livers from female rats compared with males. Hepatic elongase 6 mRNA and protein were 5.9- and 2.0-fold higher, respectively, in females compared with males. Stearoyl-CoA desaturase expression did not differ. Specific hormonal effects were examined in HepG2 cells cultured with varying concentrations of 17β-estradiol, progesterone and testosterone (0, 10, 30 and 100 nM) for 72 h. Progesterone and 17β-estradiol treatments increased, while testosterone decreased, elongase 6 protein. Sex differences in MUFA composition were associated with increased expression of hepatic elongase 6 in females relative to male rats, which appears to be mediated by sex hormones based on observations of hormonal treatments of HepG2 cells. Content Type Journal Article Category Research Paper Pages 1-11 DOI 10.1007/s12263-012-0325-3 Authors Kristin A. Marks, Laboratory of Nutritional and Nutraceutical Research, Department of Kinesiology, University of Waterloo, Waterloo, ON N2L 3G1, Canada Alex P. Kitson, Laboratory of Nutritional and Nutraceutical Research, Department of Kinesiology, University of Waterloo, Waterloo, ON N2L 3G1, Canada Ken D. Stark, Laboratory of Nutritional and Nutraceutical Research, Department of Kinesiology, University of Waterloo, Waterloo, ON N2L 3G1, Canada Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932

Description:    Prolonged high-fat diet leads to the development of obesity and multiple comorbidities including non-alcoholic steatohepatitis (NASH), but the underlying molecular basis is not fully understood. We combine molecular networks and time course gene expression profiles to reveal the dynamic changes in molecular networks underlying diet-induced obesity and NASH. We also identify hub genes associated with the development of NASH. Core diet-induced obesity networks were constructed using Ingenuity pathway analysis (IPA) based on 332 high-fat diet responsive genes identified in liver by time course microarray analysis (8 time points over 24 weeks) of high-fat diet-fed mice compared to normal diet-fed mice. IPA identified five core diet-induced obesity networks with time-dependent gene expression changes in liver. These networks were associated with cell-to-cell signaling and interaction (Network 1), lipid metabolism (Network 2), hepatic system disease (Network 3 and 5), and inflammatory response (Network 4). When we merged these core diet-induced obesity networks, Tlr2, Cd14, and Ccnd1 emerged as hub genes associated with both liver steatosis and inflammation and were altered in a time-dependent manner. Further, protein–protein interaction network analysis revealed Tlr2, Cd14, and Ccnd1 were interrelated through the ErbB/insulin signaling pathway. Dynamic changes occur in molecular networks underlying diet-induced obesity. Tlr2, Cd14, and Ccnd1 appear to be hub genes integrating molecular interactions associated with the development of NASH. Therapeutics targeting hub genes and core diet-induced obesity networks may help ameliorate diet-induced obesity and NASH. Content Type Journal Article Category Research Paper Pages 1-16 DOI 10.1007/s12263-012-0322-6 Authors Hea-Young Oh, Division of Biosystems Research, Green Bio Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 111 Gwahangno, Yuseong-gu, Daejeon, 305-806 Republic of Korea Su-kyung Shin, Department of Food Science and Nutrition, Center for Food and Nutritional Genomics Research, Kyungpook National University, 1370 Sank-Yuk Dong Puk-Ku, Daegu, 702-701 Republic of Korea Hyoung-Sam Heo, Division of Biosystems Research, Green Bio Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 111 Gwahangno, Yuseong-gu, Daejeon, 305-806 Republic of Korea Ji-Sook Ahn, Division of Biosystems Research, Green Bio Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 111 Gwahangno, Yuseong-gu, Daejeon, 305-806 Republic of Korea Eun-Young Kwon, Department of Food Science and Nutrition, Center for Food and Nutritional Genomics Research, Kyungpook National University, 1370 Sank-Yuk Dong Puk-Ku, Daegu, 702-701 Republic of Korea Jung Han Yoon Park, Department of Food Science and Nutrition, College of Natural Sciences, Hallym University, Chuncheon, 200-702 Republic of Korea Yun-young Cho, Department of Food Science and Nutrition, Center for Food and Nutritional Genomics Research, Kyungpook National University, 1370 Sank-Yuk Dong Puk-Ku, Daegu, 702-701 Republic of Korea Hae-Jin Park, Department of Food Science and Nutrition, Center for Food and Nutritional Genomics Research, Kyungpook National University, 1370 Sank-Yuk Dong Puk-Ku, Daegu, 702-701 Republic of Korea Mi-Kyung Lee, Department of Food Science and Nutrition, Sunchon National University, Sunchon, Republic of Korea Eun Jung Kim, Department of Food Science and Nutrition, Daegu Catholic University, Gyeongsan, Republic of Korea Un-Ju Jung, Department of Food Science and Nutrition, Center for Food and Nutritional Genomics Research, Kyungpook National University, 1370 Sank-Yuk Dong Puk-Ku, Daegu, 702-701 Republic of Korea Robin A. McGregor, Department of Food Science and Nutrition, Center for Food and Nutritional Genomics Research, Kyungpook National University, 1370 Sank-Yuk Dong Puk-Ku, Daegu, 702-701 Republic of Korea Cheol-Goo Hur, Division of Biosystems Research, Green Bio Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 111 Gwahangno, Yuseong-gu, Daejeon, 305-806 Republic of Korea Myung-Sook Choi, Department of Food Science and Nutrition, Center for Food and Nutritional Genomics Research, Kyungpook National University, 1370 Sank-Yuk Dong Puk-Ku, Daegu, 702-701 Republic of Korea Journal Genes & Nutrition Online ISSN 1865-3499 Print ISSN 1555-8932