ALBERT

Description: Nutritional systems biology is an evolving research field aimed at understanding nutritional processes at a systems level. It is known that the development of cancer can be influenced by the nutritional status, and the link between vitamin D status and different cancer types is widely investigated. In this study, we performed an integrative network-based analysis using a publicly available data set studying the role of 1,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ) in prostate cancer cells on mRNA and microRNA level. Pathway analysis revealed 15 significantly altered pathways: eight more general mostly cell cycle-related pathways and seven cancer-specific pathways. The changes in the G1-to-S cell cycle pathway showed that 1,25(OH) 2 D 3 down-regulates the genes influencing the G1-to-S phase transition. Moreover, after 1,25(OH) 2 D 3 treatment the gene expression in several cancer-related processes was down-regulated. The more general pathways were merged into one network and then extended with known protein–protein and transcription factor–gene interactions. Network algorithms were used to (1) identify active network modules and (2) integrate microRNA regulation in the network. Adding microRNA regulation to the network enabled the identification of gene targets of significantly expressed microRNAs after 1,25(OH) 2 D 3 treatment. Six of the nine differentially expressed microRNAs target genes in the extended network, including CLSPN , an important checkpoint regulator in the cell cycle that was down-regulated, and FZD5 , a receptor for Wnt proteins that was up-regulated. The extendable network-based tools PathVisio and Cytoscape enable straightforward, in-depth and integrative analysis of mRNA and microRNA expression data in 1,25(OH) 2 D 3 -treated cancer cells.

Description: The aim of the study was to assess the relationship between sweet taste genes and dental caries prevalence in a large sample of adults. In addition, the association between sweet liking and sugar intake with dental caries was investigated. Caries was measured by the decayed, missing, filled teeth (DMFT) index in 647 Caucasian subjects (285 males and 362 females, aged 18–65 years), coming from six villages in northeastern Italy. Sweet liking was assessed using a 9-point scale, and the mean of the liking given by each individual to specific sweet food and beverages was used to create a sweet liking score. Simple sugar consumption was estimated by a dietary history interview, considering both added sugars and sugar present naturally in foods. Our study confirmed that polymorphisms in TAS1R2 and GLUT2 genes are related to DMFT index. In particular, GG homozygous individuals for rs3935570 in TAS1R2 gene ( p value = 0.0117) and GG homozygous individuals for rs1499821 in GLUT2 gene ( p value = 0.0273) showed higher DMFT levels compared to both heterozygous and homozygous for the alternative allele. Furthermore, while the relationship sugar intake–DMFT did not achieve statistical significance ( p value = 0.075), a significant association was identified between sweet liking and DMFT ( p value = 0.004), independent of other variables. Our study showed that sweet taste genetic factors contribute to caries prevalence and highlighted the role of sweet liking as a predictor of caries risk. Therefore, these results may open new perspectives for individual risk identification and implementation of target preventive strategies, such as identifying high-risk patients before caries development.

Description: On the basis of a scientific-philosophical analysis, this paper tries to show that the approaches in current nutritional science—including its subdisciplines which focus on molecular aspects—are predominantly application-oriented. This becomes particularly evident through a number of conceptual problems characterized by the triad of ‘dearth of theoretical foundation,’ ‘particularist research questions,’ and ‘reductionist understanding of nutrition.’ The thesis presented here is that an interpretive framework based on nutritional biology is able to shed constructive light on the fundamental problems of nutritional science. In this context, the establishment of ‘nutritional biology’ as a basic discipline in research and education would be a first step toward recognizing the phenomenon of ‘nutrition’ as an oecic process as a special case of an organism–environment interaction. Modern nutritional science should be substantively grounded on ecological—and therefore systems biology as well as organismic—principles. The aim of nutritional biology, then, should be to develop near-universal ‘law statements’ in nutritional science—a task which presents a major challenge for the current science system.

Description: Polyunsaturated fatty acids (PUFAs) have a major impact on human health. Recent genome-wide association studies (GWAS) have identified several genetic loci that are associated with plasma levels of n-3 and n-6 PUFAs in primarily subjects of European ancestry. However, the relevance of these findings has not been evaluated extensively in other ethnic groups. The primary aim of this study was to evaluate for genetic loci associated with n-3 and n-6 PUFAs and to validate the role of recently identified index loci using data from a Singaporean Chinese population. Using a GWAS approach, we evaluated associations with plasma concentrations of three n-3 PUFAs [alphalinolenic acid (ALA), eicosapentaenoic acid and docosahexaenoic acid], four n-6 PUFAs [linoleic acid (LA), gammalinolenic acid, dihomogammalinolenic acid (DGLA) and arachidonic acid], and estimates of delta-5 desaturase and delta-6 desaturase activities among the participants ( N  = 1361) of the Singaporean Chinese Health Study. Our results reveal robust genome-wide associations ( p value 〈5 × 10 −8 ) with ALA, all four n-6 PUFAs, and delta-6 desaturase activity at the FADS1 / FADS2 locus. We further replicated the associations between common index variants at the NTAN1 / PDXDC1 locus and n-6 PUFAs LA and DGLA, and between the JMJD1C locus and n-6 PUFA LA ( p value between 0.0490 and 9.88 × 10 −4 ). These associations were independent of dietary intake of PUFAs. In aggregate, we show that genetic loci that influence plasma concentrations of n-3 and n-6 PUFAs are shared across different ethnic groups.

Description: The extracellular matrix (ECM) of adipocytes is important for body weight regulation. Here, we investigated whether genetic variation in ECM-related genes is associated with weight regain among participants of the European DiOGenes study. Overweight and obese subjects ( n  = 469, 310 females, 159 males) were on an 8-week low-calorie diet with a 6-month follow-up. Body weight was measured before and after the diet, and after follow-up. Weight maintenance scores (WMS, regained weight as percentage of lost weight) were calculated based on the weight data. Genotype data were retrieved for 2903 SNPs corresponding to 124 ECM-related genes. Regression analyses provided us with six significant SNPs associated with the WMS in males: 3 SNPs in the POSTN gene and a SNP in the LAMB1 , COL23A1, and FBLN5 genes. For females, 1 SNP was found in the FN1 gene. The risk of weight regain was increased by: the C/C genotype for POSTN in a co-dominant model (OR 8.25, 95 % CI 2.85–23.88) and the T/C–C/C genotype in a dominant model (OR 4.88, 95 % CI 2.35–10.16); the A/A genotype for LAMB1 both in a co-dominant model (OR 18.43, 95 % CI 2.35–144.63) and in a recessive model (OR 16.36, 95 % CI 2.14–124.9); the G/A genotype for COL23A1 in a co-dominant model (OR 3.94, 95 % CI 1.28–12.10), or the A-allele in a dominant model (OR 2.86, 95 % CI 1.10–7.49); the A/A genotype for FBLN5 in a co-dominant model (OR 13.00, 95 % CI 1.61–104.81); and the A/A genotype for FN1 in a recessive model (OR 2.81, 95 % CI 1.40–5.63). Concluding, variants of ECM genes are associated with weight regain after weight loss in a sex-specific manner.

Description: Induction of skeletal muscle (SM) mitochondrial stress by expression of uncoupling protein 1 (UCP1) in mice results in a healthy metabolic phenotype associated with increased secretion of FGF21 from SM. Here, we investigated whether SM mitochondrial uncoupling can compensate obesity and insulin resistance in the NZO mouse, a polygenic diabesity model. Male NZO mice were crossed with heterozygous UCP1 transgenic (tg) mice (mixed C57BL/6/CBA background) and further backcrossed to obtain F1 and N2 offspring with 50 and 75 % NZO background, respectively. Male F1 and N2 progeny were fed a high-fat diet ad libitum for 20 weeks from weaning. Blood glucose was reduced, and diabetes (severe hyperglycemia 〉300 mg/dl) was fully prevented in both F1- and N2-tg progeny compared to a diabetes prevalence of 15 % in F1 and 42 % in N2 wild type. In contrast, relative body fat content and plasma insulin were decreased, and glucose tolerance was improved, in F1-tg only. Both F1 and N2-tg showed decreased lean body mass. Accordingly, induction of SM stress response including FGF21 expression and secretion was similar in both F1 and N2-tg mice. In white adipose tissue, expression of FGF21 target genes was enhanced in F1 and N2-tg mice, whereas lipid metabolism genes were induced in F1-tg only. There was no evidence for induction of browning in either UCP1 backcross. We conclude that SM mitochondrial uncoupling induces FGF21 expression and prevents diabetes in mice with a 50–75 % NZO background independent of its effects on adipose tissue.

Description: An iron-deficient rat model was established and used to determine the effects of different iron sources on iron metabolism and absorption. Iron-deficient rats were assigned to one of three treatment groups, and their diet was supplemented with deionized water (control), Fe-CGly, or FeSO 4 for 8 days via intragastric administration. Blood samples were obtained for analysis of iron-related properties, and the small intestine and liver were removed for quantitative reverse transcription PCR of genes related to iron metabolism. The serum total iron-binding capacity (TIBC) levels of rats in Fe-CGly and FeSO 4 supplementation groups was lower ( P  〈 0.05) than that of the rats in the control group. The rats in Fe-CGly group exhibited higher ( P  〈 0.05) plasma Fe and ferritin levels and lower ( P  〈 0.05) TIBC levels compared with the rats in FeSO 4 groups. The relative expression of liver hepcidin increased ( P  〈 0.05) by tenfold and 80-fold in the Fe-CGly and FeSO 4 groups, respectively, whereas divalent metal transporter 1, duodenal cytochrome b , and ferroportin 1 expression decreased ( P  〈 0.05) in the duodenum in both Fe-CGly and FeSO 4 group. A comparison between Fe-CGly and FeSO 4 group showed that iron regulatory protein 1 ( IRP1 ) and iron regulatory protein ( IRP2 ) expressions were reduced ( P  〈 0.05) in rats administered FeSO 4 than in rats administered with Fe-Cgly. These results indicate that Fe-CGly rapidly improves the blood iron status and that IRP1 and IRP2 may play an important role in the intestinal absorption of Fe-CGly.

Description: The incidence of iron deficiency anemia in pregnancy is high in India where iron supplementation is a regular practice. The response to oral iron is influenced by several factors such as age, body mass index, gravida, socioeconomic status, food, vitamin deficiency and compliance to supplements. The major challenge is to understand the various modulators of iron status in this high-risk group so that we can improve the diagnosis and the management of these patients. The current study was designed to evaluate the iron status during pregnancy and to identify factors which might be influencing their response to oral iron. We investigated a total of 181 pregnant women with anemia (Hb 〈 11 g/dl) and evaluated the impact of probable factors on anemia and their iron status. Assessment of the response was based on hemoglobin and serum ferritin or transferrin saturation level after 8 and 20 weeks of iron supplementation. Socioeconomic, clinical, hematological, biochemical and genetic factors were all evaluated. Molecular analysis revealed that HFE variant allele (G) (rs1799945) was significantly associated with an adequate response to iron supplementation. We identified five subjects with a sustained poor response, and targeted re-sequencing of eleven iron-related genes was performed in them. We have identified seven novel variants in them, and in silico analysis suggested that these variants may have an iron regulatory effect. Taken together, our findings underscore the association of genetic variants with response to supplements in pregnancy, and they can be extended to other diseases where anemia and iron deficiency coexist.

Description: Dietary flavonoid intake is associated with reduced risk of cardiovascular diseases, possibly by affecting metabolic health. The relative potency of different flavonoids in causing beneficial effects on energy and lipid metabolism has not been investigated. Effects of quercetin, hesperetin, epicatechin, apigenin and anthocyanins in mice fed a high-fat diet (HF) for 12 weeks were compared, relative to normal-fat diet. HF-induced body weight gain was significantly lowered by all flavonoids (17–29 %), but most by quercetin. Quercetin significantly lowered HF-induced hepatic lipid accumulation (71 %). Mesenteric adipose tissue weight and serum leptin levels were significantly lowered by quercetin, hesperetin and anthocyanins. Adipocyte cell size and adipose tissue inflammation were not affected. The effect on body weight and composition could not be explained by individual significant effects on energy intake, energy expenditure or activity. Lipid metabolism was not changed as measured by indirect calorimetry or expression of known lipid metabolic genes in liver and white adipose tissue. Hepatic expression of Cyp2b9 was strongly downregulated by all flavonoids. In conclusion, all flavonoids lowered parameters of HF-induced adiposity, with quercetin being most effective.

Description: Background VAAM is an amino acid mixture that simulates the composition of Vespa larval saliva. VAAM enhanced physical endurance of mice and have been used by athletes as a supplementary drink before exercise. However, there is no information on the effect of VAAM on the physiology of freely moving animals. The purpose of this study was to obtain information about the VAAM-dependent regulation of liver and adipose tissue transcriptomes. Results Mice were orally fed a VAAM solution, an amino acid mixture mimicking casein hydrolysate (CAAM) or water under ad libitum feeding conditions for 5 days. Comparisons of the hepatic transcriptome between VAAM-, CAAM-, and water-treated groups revealed a VAAM-specific regulation of the metabolic pathway, i.e., the down-regulation of glycolysis and fatty acid oxidation and the up-regulation of polyunsaturated fatty acid synthesis and glucogenic amino acid utilization. Similar transcriptomic analyses of white and brown adipose tissues (WAT and BAT, respectively) indicated the up-regulation of phospholipid synthesis in WAT and the negative regulation of cellular processes in BAT. Because the coordinated regulation of tissue transcriptomes implied the presence of upstream signaling common to these tissues, we conducted an Ingenuity Pathways Analysis. This analysis showed that estrogenic and glucagon signals were activated in the liver and WAT and that beta-adrenergic signaling was activated in all three tissues. Conclusions We found that VAAM ingestion had an effect on multiple tissue transcriptomes of freely moving mice. Utilization of glycogenic amino acids may have been activated in the liver. Fatty acid conversion into phospholipid, not to triacylglycerol, may have been stimulated in adipocytes contrasting that a little effect was observed in BAT. Analysis of upstream factors revealed that multiple hormonal signals were activated in the liver, WAT, and BAT. Our data provide some clues to understanding the role of VAAM in metabolic regulation.

Description: Background Our previous study showed that fatty acids extract obtained from CLA-enriched egg yolks (EFA-CLA) suppressed the viability of MCF-7 cancer cell line more effectively than extract from non-enriched egg yolks (EFA). In this study, we analysed the effect of EFA-CLA and EFA on transcriptome profile of MCF-7 cells by applying the whole Human Genome Microarray technology. Results We found that EFA-CLA and EFA treated cells differentially regulated genes involved in cancer development and progression. EFA-CLA, compared to EFA, positively increased the mRNA expression of TSC2 and PTEN tumor suppressors as well as decreased the expression of NOTCH1 , AGPS , GNA12 , STAT3 , UCP2 , HIGD2A , HIF1A , PPKAR1A oncogenes. Conclusions We show for the first time that EFA-CLA can regulate genes engaged in AKT/mTOR pathway and inhibiting cell cycle progression. The observed results are most likely achieved by the combined effect of both: incorporated CLA isomers and other fatty acids in eggs organically modified through hens’ diet. Our results suggest that CLA-enriched eggs could be easily available food products with a potential of a cancer chemopreventive agent.

Description: Background Vitamin D deficiency is a well-documented public health issue with both genetic and environmental determinants. Populations living at far northern latitudes are vulnerable to vitamin D deficiency and its health sequelae, although consumption of traditional native dietary pattern rich in fish and marine mammals may buffer the effects of reduced sunlight exposure. To date, few studies have investigated the genetics of vitamin D metabolism in circumpolar populations or considered genediet interactions with fish and n-3 fatty acid intake. Methods We searched for genomic regions exhibiting linkage and association with circulating levels of vitamin D and parathyroid hormone (PTH) in 982 Yup’ik individuals from the Center for Alaska Native Health Research Study. We also investigated potential interactions between genetic variants and a biomarker of traditional dietary intake, the δ15N value. Results We identified several novel regions linked with circulating vitamin D and PTH as well as replicated a previous linkage finding on 2p16.2 for vitamin D. Bioinformatic analysis revealed multiple candidate genes for both PTH and vitamin D, including CUBN , MGAT3 , and NFKBIA . Targeted association analysis identified NEBL as a candidate gene for vitamin D and FNDC3B for PTH. We observed significant associations between a variant in MXD1 and vitamin D only when an interaction with the δ15N value was included. Finally, we integrated pathway level information to illustrate the biological validity of the proposed candidate genes. Conclusion We provide evidence of linkage between several biologically plausible genomic regions and vitamin D metabolism in a circumpolar population. Additionally, these findings suggest that a traditional dietary pattern may modulate genetic effects on circulating vitamin D.

Description: Background Cumulating evidence underlines the role of adipose tissue metallothionein (MT) in the development of obesity and type 2 diabetes. Fasting/refeeding was shown to affect MT gene expression in the rodent liver. The influence of nutritional status on MT gene expression in white adipose tissue (WAT) is inconclusive. The aim of this study was to verify if fasting and fasting/refeeding may influence expression of MT genes in WAT of rats. Results Fasting resulted in a significant increase in MT1 and MT2 gene expressions in retroperitoneal, epididymal, and inguinal WAT of rats, and this effect was reversed by refeeding. Altered expressions of MT1 and MT2 genes in all main fat depots were reflected by changes in serum MT1 and MT2 levels. MT1 and MT2 messenger RNA (mRNA) levels in WAT correlated inversely with serum insulin concentration. Changes in MT1 and MT2 mRNA levels were apparently not related to total zinc concentrations and MTF1 and Zn transporter mRNA levels in WAT. Fasting or fasting/refeeding exerted no effect on the expression of MT3 gene in WAT. Addition of insulin to isolated adipocytes resulted in a significant decrease in MT1 and MT2 gene expressions. In contrast, forskolin or dibutyryl-cAMP (dB-cAMP) enhanced the expressions of MT1 and MT2 genes in isolated adipocytes. Insulin partially reversed the effect of dB-cAMP on MT1 and MT2 gene expressions. Conclusions This study showed that the expressions of MT1 and MT2 genes in WAT are regulated by nutritional status, and the regulation may be independent of total zinc concentration.

Description: Background Mitochondria are of major importance in oocyte and early embryo, playing a key role in maintaining energy homeostasis. Epidemiological findings indicate that maternal undernutrition-induced mitochondrial dysfunction during pregnancy is associated with the development of metabolic disorders in offspring. Here, we investigated the effects of moderately decreased maternal energy intake during pregnancy on skeletal muscle mitochondrial biogenesis in fetal offspring with pig as a model. Methods Pregnant Meishan sows were allocated to a standard-energy (SE) intake group as recommended by the National Research Council (NRC; 2012) and a low-energy (LE) intake group. Fetal umbilical vein serum and longissimus muscle samples were collected for further analysis on day 90 of pregnancy. Results Sow and fetal weights and the concentrations of serum growth hormone (GH) and glucose were reduced in LE group. Maternal LE diet decreased the messenger RNA (mRNA) expression of genes involved in mitochondrial biogenesis and function such as peroxisome proliferator-activated receptor gamma coactivator 1α (PPARGC1A), nuclear respiratory factor 1 (NRF1), mitochondrial transcription factor A (TFAM), β subunit of mitochondrial H + -ATP synthase (ATB5B), sirtuin 1 (Sirt1), and citrate synthase (CS). The protein expression of PPARGC1A and Sirt1, intracellular NAD + -to-NADH ratio, and CS activity was reduced in LE group, and accordingly, mitochondrial DNA (mtDNA) content was decreased. Moreover, copper/zinc superoxide dismutase (CuZn-SOD) expression at both mRNA and protein levels and SOD and catalase (CAT) activities were reduced in LE group as well. Conclusions The observed decrease in muscle mitochondrial biogenesis and antioxidant defense capacity suggests that moderately decreased maternal energy intake during pregnancy impairs mitochondrial function in fetal pigs.

Description: Vitamin D receptor polymorphisms may predispose that not all individuals could have benefits from the nutritional supplementation of 25-hydroxyvitamin D. Furthermore, vitamin D-related cardiovascular effects may also be influenced by soy isoflavones considered endocrine regulators of cardiovascular homeostasis. To find possible gene–diet interactions by evaluating individualized lipid metabolism benefits from an increase in soy and 25-hydroxyvitamin D intake, 106 healthy individuals, genotyped for vitamin D receptor (VDR) gene polymorphism rs1544410 (BsmI) were randomly assigned to either no intake, to daily 250 mL or 500 mL of a 25-hydroxyvitamin D supplemented SB for 2 months. The soybean beverage induced differences in cardiovascular risk factors (lipid profile, blood pressure, TNFα and MCP-1), as well as vitamin D metabolites in a dose-gene-dependent relation. Thus, VDR BsmI polymorphism affected individual response being the GG genotype the ones that showed dose-dependent manner responsiveness in the reduction in total cholesterol, LDL and triglycerides in comparison with the AA/AG genotype. These differences were associated with increased plasma levels of 1α,25-dyhydroxyvitamin D3 in the carriers of the GG genotype. It was concluded that metabolic response to 25-hydroxyvitamin D and soybean supplementation is dependent on VDR BsmI GG genotype due to a higher conversion rate from vitamin D precursors.

Description: Long-term fructose consumption has been shown to evoke leptin resistance, to elevate triglyceride levels and to induce insulin resistance and hepatic steatosis. Autophagy has been suggested to function in processes such as lipid storage in adipose tissue and inflammation in liver. Autophagy and the leptin system have also been suggested to regulate each other. This study aimed to identify the changes caused by fetal undernourishment and postnatal fructose diet in the gene expression of leptin, its receptors (LEPR-a, LEPR-b, LEPR-c, LEPR-e and LEPR-f) and autophagy genes in the white adipose tissue (WAT) and liver of adult male rats in order to clarify the mechanism behind the metabolic alterations. The data clearly revealed that the long-term postnatal fructose diet decreased leptin levels ( p  〈 0.001), LEPR ( p  〈 0.001), especially LEPR-b ( p  = 0.011) and LEPR-f ( p  = 0.005), as well as SOCS3 ( p  〈 0.001), ACC ( p  = 0.006), ATG7 ( p  〈 0.001), MAP1LC3β ( p  〈 0.001) and LAMP2 ( p  = 0.004) mRNA expression in WAT. Furthermore, LEPR ( p  〈 0.001), especially LEPR-b ( p  = 0.001) and LEPR-f ( p  〈 0.001), ACC ( p  = 0.010), ATG7 ( p  = 0.024), MAP1LC3β ( p  = 0.003) and LAMP2 ( p  〈 0.001) mRNA expression in the liver was increased in fructose-fed rats. In addition, the LEPR expression in liver and MAP1LC3β expression in WAT together explained 55.7 % of the variation in the plasma triglyceride levels of the rats ( R adj. 2  = 0.557, p  〈 0.001). These results, together with increased p62 levels in WAT ( p  〈 0.001), could indicate decreased adipose tissue lipid storing capacity as well as alterations in liver metabolism which may represent a plausible mechanism through which fructose consumption could disturb lipid metabolism and result in elevated triglyceride levels.

Description: It is becoming increasingly apparent that responsiveness to dietary fat composition is heterogeneous and dependent on the genetic make-up of the individual. The aim of this study was to evidence a genotype-related differential effect of n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA) on the modulation of hepatic genes involved in cholesterol metabolism. Fourteen spontaneously hypertensive (SH) rats, which present a naturally occurring variation in the gene encoding for sterol responsive element binding protein 1 (SREBP-1), contributing to their inherited variation in lipid metabolism, and 14 Wistar-Kyoto (WK) rats were fed a control diet or an n-3 LC-PUFA enriched diet for 90 days. Plasma lipid profile, total lipid fatty acid composition in plasma and liver, and the expression of SREBP-1 and 2, 3-hydroxy-3-methyl-glutaryl-CoA reductase, low-density lipoprotein receptor, and acyl-CoA:cholesterol acyltransferase 2 encoding genes and proteins were determined. The positive effect of the enriched diet on the serum lipid profile, particularly on total cholesterol and triglyceride level, was clearly evidenced in both WK and SH rats, but n-3 LC-PUFA acted through a different modulation of gene and protein expression that appeared related to the genetic background. Our study evidences a different transcriptional effect of specific nutrients related to genetic variants.

Description: Worldwide, the incidence of obesity has increased dramatically over the past decades. More knowledge about the complex etiology of obesity is needed in order to find additional approaches for treatment and prevention. Investigating the exome sequencing data of 30 extremely obese subjects (BMI 45–65 kg/m 2 ) shows that predicted damaging missense variants in olfactory receptor genes on chromosome 1q and rare predicted damaging variants in the protocadherin (PCDH) beta-cluster genes on chromosome 5q31, reported in our previous work, co-localize in subjects with extreme obesity. This implies a synergistic effect between genetic variation in these gene clusters in the predisposition to extreme obesity. Evidence for a general involvement of the olfactory transduction pathway on itself could not be found. Bioinformatic analysis indicates a specific involvement of the PCDH beta-cluster genes in controlling tissue development. Further mechanistic insight needs to await the identification of the ligands of the 1q olfactory receptors. Eventually, this may provide the possibility to manipulate food flavor in a way to reduce the risk of overeating and of extreme obesity in genetically predisposed subjects.

Description: High dietary intakes and high blood levels of β-carotene are associated with a decreased incidence of various cancers. The anticancer effect of β-carotene is related to its pro-oxidant activity. DNA repair Ku proteins, as a heterodimer of Ku70 and Ku80, play a crucial role in DNA double-strand break repair. Reductions in Ku70/80 contribute to apoptosis. Previously, we showed that reactive oxygen species (ROS) activate caspase-3 which induces degradation of Ku proteins. In the present study, we investigated the mechanism of β-carotene-induced apoptosis of gastric cancer AGS cells by determining cell viability, DNA fragmentation, apoptotic indices (increases in cytochrome c and Bax, decrease in Bcl-2), ROS levels, mitochondrial membrane potential, caspase-3 activity, Ku70/80 levels, and Ku-DNA-binding activity of the cells treated with or without antioxidant N -acetyl cysteine and caspase-3 inhibitor z-DEVED-fmk. As a result, β-carotene induced apoptosis (decrease in cell viability, increases in DNA fragmentation and apoptotic indices) and caspase-3 activation, but decreased Ku70/80 levels and Ku-DNA-binding activity. β-Carotene-induced alterations (increase in caspase-3 activity, decrease in Ku proteins) and apoptosis were inhibited by N -acetyl cysteine and z-DEVED-fmk. Increment of intracellular and mitochondrial ROS levels and loss of mitochondrial membrane potential were suppressed by N -acetyl cysteine, but not by z-DEVED-fmk in β-carotene-treated cells. Therefore, β-carotene-induced increases in ROS and caspase-3 activity may lead to reduction of Ku70/80 levels, which results in apoptosis in gastric cancer cells. Loss of Ku proteins might be the underlying mechanism for β-carotene-induced apoptosis in gastric cancer cells.

Description: Single-nucleotide polymorphisms (SNPs) within genes of the one-carbon metabolism pathway have been shown to interact with dietary folate intake to modify breast cancer (BC) risk. Our group has previously demonstrated that the Mediterranean dietary pattern, rich in beneficial one-carbon metabolism micronutrients, protects against BC in Greek-Cypriot women. We aimed to investigate whether SNPs in the MTHFR (rs1801133 and rs1801131) and MTR (rs1805087) genes modify the effect of the Mediterranean dietary pattern on BC risk. Dietary intake data were obtained using a 32-item food-frequency questionnaire. A dietary pattern specific to the Greek-Cypriot population, which closely resembles the Mediterranean diet, was derived using principal component analysis (PCA) and used as our dietary variable. Genotyping was performed on subjects from the MASTOS study, a case–control study of BC in Cyprus, using TaqMan assays. Adjusted odds ratios (ORs) were estimated using logistic regression analyses. High adherence to the PCA-derived Mediterranean dietary pattern further reduced BC risk with increasing number of variant MTHFR 677T alleles (OR Q4vs.Q1 for 677TT = 0.37, 95 % CI 0.20–0.69, for 677 CT = 0.60, 95 % CI 0.42–0.86). Additionally, high adherence to the Mediterranean dietary pattern decreased BC risk in subjects with at least one MTR 2756A allele (OR Q4vs.Q1 for 2756AA = 0.59, 95 % CI 0.43–0.81, for 2756AG = 0.59, 95 % CI 0.39–0.91) and in subjects with the MTHFR 1298CC genotype (OR Q4vs.Q1 0.44, 95 % CI 0.30–0.65). Overall P -interaction values, however, were not statistically significant. Our study suggests that these MTHFR and MTR SNPs may act as effect modifiers, highlighting their biological significance in the association between Mediterranean diet, the one-carbon metabolism pathway and BC.

Description: Data on the effect of combined genetic polymorphisms, involved in folate metabolism, on the concentration of serum folate after folic acid supplementation are scarce. Therefore, we investigated the impact of seven gene polymorphisms on the concentration of serum folate and p-tHcy in healthy subjects after short-term folic acid supplementation. In a randomized, double blind, crossover study, apparently healthy subjects were given either 0.8 mg folic acid per day ( n  = 46) or placebo ( n  = 45) for 14 days. The washout period was 14 days. Fasting blood samples were collected on day 1, 15, 30 and 45. Data on subjects on folic acid supplementation ( n  = 91) and on placebo ( n  = 45) were used for the statistical analysis. The concentration of serum folate increased higher in subjects with higher age (53.5 ± 7.0 years) than in subjects with lower age (24.3 ± 3.2 years) after folic acid supplementation ( p  = 0.006). The baseline concentration of serum folate in subjects with polymorphism combination, reduced folate carrier protein, RFC1-80 GA and methylenetetrahydrofolate reductase, MTHFR677 CT+TT, was lower than RFC1-80 AA and MTHFR677 CT+TT ( p  = 0.002). After folic acid supplementation, a higher increase in the concentration of serum folate was detected in subjects with polymorphism combination RFC1-80 GA and MTHFR677 CC than RFC1-80 GG and MTHFR CT+TT combination ( p  〈 0.0001). The baseline concentration of plasma total homocysteine (p-tHcy) was altered by combined polymorphisms in genes associated with folate metabolism. After folic acid supplementation, in subjects with combined polymorphisms in methylenetetrahydrofolate dehydrogenase, MTHFD1-1958 and MTHFR-677 genes, the concentration of p-tHcy was changed ( p  = 0.002). The combination of RFC1-80 and MTHFR-677 polymorphisms had a profound affect on the concentration of serum folate in healthy subjects before and after folic acid supplementation.

Description: Human and companion animal health depends upon nutritional quality of foods. Seed varieties, seasonal and local growing conditions, transportation, food processing, and storage, and local food customs can influence the nutrient content of food. A new and intensive area of investigation is emerging that recognizes many factors in these agri-food systems that influence the maintenance of nutrient quality which is fundamental to ensure nutrient security for world populations. Modeling how these systems function requires data from different sectors including agricultural, environmental, social, and economic, but also must incorporate basic nutrition and other biomedical sciences. Improving the agri-food system through advances in pre- and post-harvest processing methods, biofortification, or fortifying processed foods will aid in targeting nutrition for populations and individuals. The challenge to maintain and improve nutrient quality is magnified by the need to produce food locally and globally in a sustainable and consumer-acceptable manner for current and future populations. An unmet requirement for assessing how to improve nutrient quality, however, is the basic knowledge of how to define health. That is, health cannot be maintained or improved by altering nutrient quality without an adequate definition of what health means for individuals and populations. Defining and measuring health therefore becomes a critical objective for basic nutritional and other biomedical sciences.

Description: Background MicroRNAs (miRNAs) are small non-coding RNAs involved in the modulation of gene expression and in the control of numerous cell functions. Alterations of miRNA patterns frequently occur in cancer and metabolic disorders, including obesity. Recent studies showed remarkable stability of miRNAs in both plasma and serum making them suitable as potential circulating biomarkers for a variety of diseases and conditions. The aim of this study was to assess the profile of circulating miRNAs expressed in plasma samples of overweight or obese (OW/Ob) and normal weight (NW) prepubertal children from a European cohort ( www.ifamilystudy.eu ). The project, aimed to assess the determinants of eating behavior in children and adolescents of eight European countries, is built on the IDEFICS cohort ( www.ideficsstudy.eu ), established in 2006. Among the participants of the I.Family Italian Cohort, ten OW/Ob (age 10.7 ± 1.5 years, BMI 31.6 ± 4.3 kg/m 2 ) and ten NW (age 10.5 ± 2.7 years, BMI 16.4 ± 1.7 kg/m 2 ) children were selected for the study. Gene arrays were employed to differentially screen the expression of 372 miRNAs in pooled plasma samples. Deregulated miRNAs ( p  〈 0.05) were further validated in the individual samples using a real-time PCR (RT-qPCR) approach. Results Using a significance threshold of p  〈 0.05 and a fold-change threshold of ± 4.0, we preliminarily identified in the pooled samples eight miRNAs that differed between the OW/Ob and NW groups. The validation by RT-qPCR in the individual plasma samples showed a twofold upregulation of miR-31-5p, a threefold upregulation of miR-2355-5p, and a 0.5-fold downregulation of miR-206 in OW/Ob as compared with NW. The molecular functions of these differentially expressed plasma miRNAs as well as their expected mRNA targets were predicted by bioinformatics tools. Conclusions This pilot study shows that three circulating miRNAs are differentially regulated in OW/Ob as compared with NW children. Although causal pathways cannot be firmly inferred by these results, that deserve confirmation in larger samples, it is conceivable that circulating miRNAs may be novel biomarkers of obesity and related metabolic disturbances.

Description: Background TCF7L2 is a central transcription factor in the canonical wingless-type MMTV integration site (WNT) signaling pathway, and genetic variants in TCF7L2 have been found to interact with dietary fiber intake on type 2 diabetes risk. Here, we investigate whether other type 2 diabetes genes could be involved in the WNT signaling pathway and whether variants in such genes might interact with dietary fiber on type 2 diabetes incidence. Results We included 26,905 individuals without diabetes from the Malmö Diet and Cancer Study cohort. Diet data was collected at baseline using a food frequency questionnaire, a 7-day food record, and an interview. Altogether, 51 gene loci were analyzed for putative links to WNT signaling. Over a mean follow-up period of 14.7 years, 3132 incident cases of type 2 diabetes were recorded. Seven genes (nine single nucleotide polymorphisms (SNPs)) were annotated as involved in WNT signaling including TCF7L2 (rs7903146 and rs12255372), HHEX (rs1111875), HNF1A (rs7957197), NOTCH2 (rs10923931), TLE4 (rs13292136), ZBED3 (rs4457053), and PPARG (rs1801282 and rs13081389). SNPs in TCF7L2 , NOTCH2 , and ZBED3 showed significant interactions with fiber intake on type 2 diabetes incidence ( P interaction  = 0.034, 0.005, 0.017, and 0.002, respectively). The magnitude of the association between the TCF7L2 risk allele and incident type 2 diabetes increased from the lowest to the highest quintiles of fiber intake. Higher fiber associated with lower type 2 diabetes risk only among risk allele carriers of the NOTCH2 variant and homozygotes of the risk allele of the ZBED3 variant. Conclusions Our results suggest that several type 2 diabetes susceptibility SNPs in genes involved in WNT signaling may interact with dietary fiber intake on type 2 diabetes incidence.

Description: 〈h3〉Abstract〈/h3〉 〈p〉Decline of cellular functions especially cognitive is a major deficit that arises with age in humans. Harnessing the strengths of small and genetic tractable model systems has revealed key conserved regulatory biochemical and signaling pathways that control aging. Here, we review some of the key signaling and biochemical pathways that coordinate aging processes with special emphasis on 〈em〉Caenorhabditis elegans〈/em〉 as a model system and discuss how nutrients and metabolites can regulate lifespan by coordinating signaling and epigenetic programs. We focus on central nutrient-sensing pathways such as mTOR and insulin/insulin-like growth factor signaling and key transcription factors including the conserved basic helix-loop-helix transcription factor HLH-30/TFEB.〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉Seaweeds are marine macroalgae, some of which are edible. They are rich in specific dietary fibers and also contain other characteristic biological constituents. Biological activities have been investigated mainly in animal studies, while very few results are available from human studies. Biomarkers of food intake (BFIs) specific to seaweed could play an important role as objective measurements in observational studies and dietary intervention studies. Thus, the health effects of seaweeds can be explored and understood by discovering and applying BFIs.〈/p〉 〈p〉This review summarizes studies to identify candidate BFIs of seaweed intake. These BFIs are evaluated by a structured validation scheme.〈/p〉 〈p〉Hydroxytrifuhalol A, 7-hydroxyeckol, C-O-C dimer of phloroglucinol, diphloroethol, fucophloroethol, dioxinodehydroeckol, and/or their glucuronides or sulfate esters which all belong to the phlorotannins are considered candidate biomarkers for brown seaweed. Fucoxanthinol, the main metabolite of fucoxanthin, is also regarded as a candidate biomarker for brown seaweed. Further validation will be needed due to the very limited number of human studies.〈/p〉 〈p〉Further studies are also needed to identify additional candidate biomarkers, relevant specifically for the red and green seaweeds, for which no candidate biomarkers emerged from the literature search. Reliable BFIs should also ideally be found for the whole seaweed food group.〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈span〉 〈h3〉Background〈/h3〉 〈p〉The mechanism of high ambient temperature affecting meat quality is not clear till now. This study investigated the effect of high ambient temperature on meat quality and nutrition metabolism in finishing pigs.〈/p〉 〈/span〉 〈span〉 〈h3〉Methods〈/h3〉 〈p〉All pigs received the same corn-soybean meal diet. A total of 24 Landrace × Large White pigs (60 kg BW, all were female) were assigned to three groups: 22AL (fed ad libitum at 22 °C), 35AL (ad libitum fed at 35 °C), and 22PF (at 22 °C, but fed the amount consumed by pigs raised at 35 °C) and the experiment lasted for 30 days.〈/p〉 〈/span〉 〈span〉 〈h3〉Results〈/h3〉 〈p〉Feed intake, weight gain, and intramuscular fat (IMF) content of pigs were reduced, both directly by high temperature and indirectly through reduced feed intake. Transcriptome analysis of longissimus dorsi (LM) showed that downregulated genes caused by feed restriction were mainly involved in muscle development and energy metabolism; and upregulated genes were mainly involved in response to nutrient metabolism or extracellular stimulus. Apart from the direct effects of feed restriction, high temperature negatively affected the muscle structure and development, energy, or catabolic metabolism, and upregulated genes were mainly involved in DNA or protein damage or recombination, cell cycle process or biogenesis, stress response, or immune response.〈/p〉 〈/span〉 〈span〉 〈h3〉Conclusion〈/h3〉 〈p〉Both high temperature and reduced feed intake affected growth performance and meat quality. Apart from the effects of reducing feed intake, high temperature per se negatively downregulated cell cycle and upregulated heat stress response. High temperature also decreased the energy or catabolic metabolism level through PPAR signaling pathway.〈/p〉 〈/span〉

Description: 〈h3〉Abstract〈/h3〉 〈span〉 〈h3〉Background〈/h3〉 〈p〉High protein intake may promote angiogenesis giving support to the development of metastasis according to the experimental data. However, nutritional epidemiologic evidence is inconsistent with metastasis. Therefore, we aimed to study the association between dietary intake of protein and tumoral expression levels of 〈em〉Ras homologous gene family member A〈/em〉 (〈em〉RhoA〈/em〉), 〈em〉vascular endothelial growth factor-A〈/em〉 (〈em〉VEGF-A〈/em〉), and 〈em〉VEGF receptor-2〈/em〉 (〈em〉VEGFR2〈/em〉) in primary breast cancer (BC) patients.〈/p〉 〈/span〉 〈span〉 〈h3〉Methods〈/h3〉 〈p〉Over this consecutive case series, 177 women primary diagnosed with histopathologically confirmed BC in Tabriz (Iran) were enrolled between May 2011 and November 2016. A validated food frequency questionnaire was completed for eligible participants. Fold change in gene expression was measured using quantitative real-time PCR. Principal component factor analysis (PCA) was used to express dietary groups of proteins.〈/p〉 〈/span〉 〈span〉 〈h3〉Results〈/h3〉 〈p〉Total protein intake was associated with the expression level of 〈em〉VEGF-A〈/em〉 in progesterone receptor-positive (PR+: 〈em〉β〈/em〉 = 0.296, 〈em〉p〈/em〉 〈 0.01) and 〈em〉VEGFR2〈/em〉 in patients with involvement of axillary lymph node metastasis (ALNM+: 〈em〉β〈/em〉 = 0.295, 〈em〉p〈/em〉 〈 0.01) when covariates were adjusted. High animal protein intake was correlated with overexpression of 〈em〉RhoA〈/em〉 in tumors with estrogen receptor-positive (ER+: 〈em〉β〈/em〉 = 0.230, 〈em〉p〈/em〉 〈 0.05), ALNM+ (〈em〉β〈/em〉 = 0.238, 〈em〉p〈/em〉 〈 0.05), and vascular invasion (VI+: 〈em〉β〈/em〉 = 0.313, 〈em〉p〈/em〉 〈 0.01). Animal protein intake was correlated with the overexpression of 〈em〉VEGFR2〈/em〉 when tumors were positive for hormonal receptors (ER+: 〈em〉β〈/em〉 = 0.299, 〈em〉p〈/em〉 〈 0.01; PR+: 〈em〉β〈/em〉 = 0.296, 〈em〉p〈/em〉 〈 0.01). Based on the PCA outputs, protein provided by whole meat (white and red meat) was associated inversely with 〈em〉RhoA〈/em〉 expression in ALNM+ (〈em〉β〈/em〉 = − 0.253, 〈em〉p〈/em〉 〈 0.05) and premenopausal women (〈em〉β〈/em〉 = − 0.285, 〈em〉p〈/em〉 〈 0.01) in adjusted models. Whole meat was correlated with 〈em〉VEGFR2〈/em〉 overexpression in VI+ (〈em〉β〈/em〉 = 0.288, 〈em〉p〈/em〉 〈 0.05) and premenopausal status (〈em〉β〈/em〉 = 0.300, 〈em〉p〈/em〉 〈 0.05) in adjusted models. A group composed of dairy products and legumes was correlated with the overexpression of 〈em〉RhoA〈/em〉 (〈em〉β〈/em〉 = 0.249, 〈em〉p〈/em〉 〈 0.05) and 〈em〉VEGF-A〈/em〉 (〈em〉β〈/em〉 = 0.297, 〈em〉p〈/em〉 〈 0.05) in VI+.〈/p〉 〈/span〉 〈span〉 〈h3〉Conclusions〈/h3〉 〈p〉Based on the multivariate findings, the dietary protein could associate with the overexpression of 〈em〉RhoA〈/em〉 and 〈em〉VEGF-VEGFR2〈/em〉 in favor of lymphatic and vascular metastasis in BC patients.〈/p〉 〈/span〉

Description: 〈h3〉Abstract〈/h3〉 〈span〉 〈h3〉Background〈/h3〉 〈p〉Japan is traditionally a country with one of the highest levels of fish consumption worldwide, although the westernization of the Japanese diet has resulted in the reduction of fish consumption. A recent meta-analysis of genome-wide association studies (GWASs) on Western populations has identified a single nucleotide polymorphism (SNP) associated with fish intake frequency. Here, we examined the genetic basis for fish intake frequency among Japanese individuals.〈/p〉 〈/span〉 〈span〉 〈h3〉Results〈/h3〉 〈p〉We conducted a meta-analysis of a GWAS including 12,603 Japanese individuals and identified a susceptibility locus for fish intake frequency at 12q24 (lead variant was rs11066015, 〈em〉P〈/em〉 = 5.4 × 10〈sup〉−11〈/sup〉). rs11066015 was in a strong linkage disequilibrium with rs671, a well-known SNP related to alcohol metabolism. When adjusted for alcohol drinking, the association between rs11066015 and fish intake frequency was substantially attenuated. Subgroup analysis revealed that the effect of the 12q24 variant on fish intake frequency was stronger in males than in females (〈em〉P〈/em〉 for interaction = 0.007) and stronger in the older subgroup than in the younger subgroup (〈em〉P〈/em〉 for interaction = 0.006).〈/p〉 〈/span〉 〈span〉 〈h3〉Conclusions〈/h3〉 〈p〉Our findings suggest that the 12q24 locus is associated with fish intake frequency via alcohol drinking. This study can help contribute to personalized nutrition information, suggesting that fish intake should be promoted to consumers who have the rs11066015 minor allele, which is genetically linked to low fish intake frequency, especially in male and older individuals.〈/p〉 〈/span〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉〈em〉Allium〈/em〉 vegetables are widely consumed around the world and are known for their potential bioactive components improving human health. These effects have been extensively investigated; however, the results were inconsistent in human studies. Biomarkers of food intake (BFIs) could provide objective measurements of food intake in observational studies and assess compliance in intervention studies. Therefore, the discovery and application of BFIs for 〈em〉Allium〈/em〉 vegetables would facilitate the exploring and understanding of the health benefit of 〈em〉Allium〈/em〉 vegetables. In this manuscript, we reviewed the currently used and potential candidate BFIs for 〈em〉Allium〈/em〉 vegetables and evaluated their levels of validation. 〈em〉S〈/em〉-Allylmercapturic acid (ALMA), allyl methyl sulfide (AMS), allyl methyl sulfoxide (AMSO), allyl methyl sulfone (AMSO〈sub〉2〈/sub〉), and 〈em〉S〈/em〉-allylcysteine (SAC), which are derived from organosulfur compounds, were shown to be promising candidate BFIs for garlic consumption. Further validation is needed to assess their robustness and concordance with other measures. Their applicability for the whole food group should be evaluated as well. 〈em〉N〈/em〉-Acetyl-〈em〉S〈/em〉-(2-carboxypropyl)cysteine (CPMA) was detected in high levels in urine after both garlic and onion intake, suggesting that it may be used for the assessment of intake of 〈em〉Allium〈/em〉 food group. The available information regarding its kinetics, robustness, and analytical performance is limited and needs to be assessed in further studies. No candidate BFIs specific to intake of onion, leek, chives, shallots, or ramsons were found. Untargeted metabolomics studies and further validation studies should be performed to discover more reliable BFIs for individual 〈em〉Allium〈/em〉 vegetables and the whole food group. This paper serves as an example of Biomarker of Food Intake Reviews (BFIRev) and biomarker of food intake validation procedures.〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈span〉 〈h3〉Background〈/h3〉 〈p〉Hypovitaminosis D is prevalent worldwide. It is more prevalent in Eastern Asia region, including Korea. In addition to various environmental factors that influence serum 25-hydroxyvitamin D (25(OH)D) concentration, genetic influence also plays a significant role based on studies estimating the heritability of 25(OH)D in non-Asian populations. The objective of this study was to determine the genetic influence on serum 25(OH)D concentration in Korean men using the twin and family data.〈/p〉 〈/span〉 〈span〉 〈h3〉Methods〈/h3〉 〈p〉A total of 1126 Korean male adult twins and family members from the Healthy Twin Study with serum 25(OH)D measurement were included in this cross-sectional study. Intraclass correlation coefficients (ICCs) and heritability were calculated by mixed linear regression analysis and quantitative genetic analysis after adjusting for environmental and lifestyle factors.〈/p〉 〈/span〉 〈span〉 〈h3〉Results〈/h3〉 〈p〉Mean (± standard deviation; SD) of serum 25(OH)D concentration was 15.34 ± 6.18 ng/ml. The prevalence of vitamin D insufficiency was 19.8% and that of vitamin D deficiency was 77.9%. After adjusting for age, the highest ICC (0.61) was observed for monozygotic twin pairs while the lowest ICC (0.31) was found for father-son pairs. Age-adjusted heritability was estimated to be 58%. When physical activity, multivitamin intake and season of blood sampling were further considered, the ICC and heritability did not materially change. In the sensitivity analysis after excluding known multivitamin users, age-adjusted heritability was reduced to 44%.〈/p〉 〈/span〉 〈span〉 〈h3〉Conclusions〈/h3〉 〈p〉In our study of Korean male twins and family members, heritability of 25(OH)D was moderately high. This supports the finding that genetic factors have significant influence on vitamin D status.〈/p〉 〈/span〉

Description: 〈h3〉Abstract〈/h3〉 〈span〉 〈h3〉Background〈/h3〉 〈p〉Microbial communities are influenced by environmental factors including host genetics. We investigated the relationship between host bitter taste receptor genotype hTAS2R38 and oral microbiota, together with the influence of geographical location.〈/p〉 〈/span〉 〈span〉 〈h3〉Methods〈/h3〉 〈p〉hTAS2R38 polymorphisms and 16S bacterial gene sequencing from oral samples were analyzed from a total of 45 healthy volunteers from different geographical locations.〈/p〉 〈/span〉 〈span〉 〈h3〉Results〈/h3〉 〈p〉Genetic variation in the bitter taste receptor TAS2R38 reflected in the microbial composition of oral mucosa in Finnish and Spanish subjects. Multivariate analysis showed significant differences in the microbial composition between country and also dependent on taste genotype. Oral microbiota was shown to be more stable to the geographical location impact among AVI-homozygotes than PAV-homozygotes or heterozygotes (PAV/AVI).〈/p〉 〈/span〉 〈span〉 〈h3〉Conclusion〈/h3〉 〈p〉Geographical location and genetic variation in the hTAS2R38 taste receptor impact oral mucosa microbial composition. These findings provide an advance in the knowledge regarding the interactions between taste receptor genes and oral microbiota. This study suggests the role of host-microbiota interactions on the food taste perception in food choices, nutrition, and eating behavior.〈/p〉 〈/span〉

Description: 〈h3〉Abstract〈/h3〉 〈span〉 〈h3〉Background〈/h3〉 〈p〉To unravel true links between diet and health, it is important that dietary exposure is accurately measured. Currently, mainly self-reporting methods (e.g. food frequency questionnaires and 24-h recalls) are used to assess food intake in epidemiological studies. However, these traditional instruments are subjective measures and contain well-known biases. Especially, estimating the intake of the group of confectionary products, such as products containing cocoa and liquorice, remains a challenge. The use biomarkers of food intake (BFIs) may provide a more objective measurement. However, an overview of current candidate biomarkers and their validity is missing for both cocoa- and liquorice-containing foods.〈/p〉 〈/span〉 〈span〉 〈h3〉Objective〈/h3〉 〈p〉The purpose of the current study was to (1) identify currently described candidate BFIs for cocoa (products) and liquorice, (2) to evaluate the validity of these identified candidate BFIs and (3) to address further validation and/or identification work to be done.〈/p〉 〈/span〉 〈span〉 〈h3〉Methods〈/h3〉 〈p〉This systematic review was based on a comprehensive literature search of three databases (PubMed, Scopus and ISI web of Science), to identify candidate BFIs. Via a second search step in the Human Metabolome Database (HMDB), the Food Database (FooDB) and Phenol-Explorer, the specificity of the candidate BFIs was evaluated, followed by an evaluation of the validity of the specific candidate BFIs, via pre-defined criteria.〈/p〉 〈/span〉 〈span〉 〈h3〉Results〈/h3〉 〈p〉In total, 37 papers were included for cocoa and 8 papers for liquorice. For cocoa, 164 unique candidate BFIs were obtained, and for liquorice, four were identified in total. Despite the high number of identified BFIs for cocoa, none of the metabolites was specific. Therefore, the validity of these compounds was not further examined. For liquorice intake, 18-glycyrrhetinic acid (18-GA) was found to have the highest assumed validity.〈/p〉 〈/span〉 〈span〉 〈h3〉Conclusions〈/h3〉 〈p〉For cocoa, specific BFIs were missing, mainly because the individual BFIs were also found in foods having a similar composition, such as tea (polyphenols) or coffee (caffeine). However, a combination of individual BFIs might lead to discriminating profiles between cocoa (products) and foods with a similar composition. Therefore, studies directly comparing the consumption of cocoa to these similar products are needed, enabling efforts to find a unique profile per product. For liquorice, we identified 18-GA as a promising BFI; however, important information on its validity is missing; thus, more research is necessary. Our findings indicate a need for more studies to determine acceptable BFIs for both cocoa and liquorice.〈/p〉 〈/span〉

Description: 〈p〉Following publication of the original article [1], the authors reported a spelling error of the third author’s name, Mar Garcia Aloy.〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈span〉 〈h3〉Background〈/h3〉 〈p〉Nearly 10 years ago, the World Health Organization reported the increasing prevalence of overweight and obesity worldwide as a challenge for public health due to the associated adverse consequences. Epidemiological studies established a firm relationship between an elevated body mass index and chronic conditions such as diabetes, dyslipidemia, hypertension, heart disease, non-alcoholic fatty liver disease, and some types of cancer. Omic studies demonstrated that microRNA (miRNA) profile changes in tissues correlate with a number of diseases, including obesity. Recent studies showed a remarkable stability of miRNAs also in blood, emphasizing their potential as theranostic agents for a variety of disorders and conditions. A number of miRNAs enriched in homeostasis of obesity and metabolic disorders have been characterized in previous researches.〈/p〉 〈/span〉 〈span〉 〈h3〉Aim〈/h3〉 〈p〉This work was finalized to investigate the differential circulating miRNAs signature in early childhood obesity. Our cross-sectional study analyzed the signature of circulating miRNAs in plasma samples of normal weight (〈em〉n〈/em〉 = 159) and overweight/obese (〈em〉n〈/em〉 = 149) children and adolescents participating to the I.Family study, an EC-funded study finalized to investigate the etiology of overweight, obesity and related disorders and the determinants of food choice, lifestyle, and related health outcomes in children and adolescents of eight European countries (〈a href="http://www.ifamilystudy.eu/"〉www.ifamilystudy.eu〈/a〉).〈/p〉 〈/span〉 〈span〉 〈h3〉Results〈/h3〉 〈p〉Differences in miRNA signature with respect to anthropometric and biochemical variables were analyzed. A high degree of variability in levels of circulating miRNAs was identified among children from different countries, in line with recent reports supporting the hypothesis that these molecules are likewise affected by environmental and lifestyle factors. A panel of miRNAs differentially expressed in overweight/low-grade obesity children was characterized (miR-551a and miR-501-5p resulted upregulated; miR-10b-5p, miR-191-3p, miR-215-5p, and miR-874-3p resulted downregulated). ROC curves were also constructed for experimentally confirmed miRNAs. Single miRNAs generally exhibited low AUC values with the highest values for miR-874-3p and miR-501-5p which in combination provided an interesting value (AUC = 0.782). Pearson’s analysis confirmed that miR-10b-5p, miR-215-5p, miR-501-5p, miR-551a, and miR-874-3p significantly correlated with BMI 〈em〉z〈/em〉-score. Molecular interactions of obesity-associated miRNAs were also predicted by bioinformatics tools.〈/p〉 〈/span〉 〈span〉 〈h3〉Conclusions〈/h3〉 〈p〉Our work showed that several circulating miRNAs are differentially represented in overweight/low-grade obesity children and adolescents. Although causal pathways cannot be firmly inferred, it is conceivable that circulating miRNAs may be new biomarkers of early childhood obesity.〈/p〉 〈/span〉 〈span〉 〈h3〉Trial registration〈/h3〉 〈p〉ISRCTN, 〈a href="http://isrctn.com/ISRCTN62310987"〉ISRCTN62310987〈/a〉. Registered 23/02/2018 - Retrospectively registered.〈/p〉 〈/span〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉Fruit is a key component of a healthy diet. However, it is still not clear whether some classes of fruit may be more beneficial than others and whether all individuals whatever their age, gender, health status, genotype, or gut microbiota composition respond in the same way to fruit consumption. Such questions require further observational and intervention studies in which the intake of a specific fruit can be precisely assessed at the population and individual levels. Within the Food Biomarker Alliance Project (FoodBAll Project) under the Joint Programming Initiative “A Healthy Diet for a Healthy Life”, an ambitious action was undertaken aiming at reviewing existent literature in a systematic way to identify validated and promising biomarkers of intake for all major food groups, including fruits. This paper belongs to a series of reviews following the same BFIRev protocol and is focusing on biomarkers of pome and stone fruit intake. Selected candidate biomarkers extracted from the literature search went through a validation process specifically developed for food intake biomarkers.〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉Dairy and egg products constitute an important part of Western diets as they represent an excellent source of high-quality proteins, vitamins, minerals and fats. Dairy and egg products are highly diverse and their associations with a range of nutritional and health outcomes are therefore heterogeneous. Such associations are also often weak or debated due to the difficulty in establishing correct assessments of dietary intake. Therefore, in order to better characterize associations between the consumption of these foods and health outcomes, it is important to identify reliable biomarkers of their intake. Biomarkers of food intake (BFIs) provide an accurate measure of intake, which is independent of the memory and sincerity of the subjects as well as of their knowledge about the consumed foods. We have, therefore, conducted a systematic search of the scientific literature to evaluate the current status of potential BFIs for dairy products and BFIs for egg products commonly consumed in Europe. Strikingly, only a limited number of compounds have been reported as markers for the intake of these products and none of them have been sufficiently validated. A series of challenges hinders the identification and validation of BFI for dairy and egg products, in particular, the heterogeneous composition of these foods and the lack of specificity of the markers identified so far. Further studies are, therefore, necessary to validate these compounds and to discover new candidate BFIs. Untargeted metabolomic strategies may allow the identification of novel biomarkers, which, when taken separately or in combination, could be used to assess the intake of dairy and egg products.〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈span〉 〈h3〉Background〈/h3〉 〈p〉Ninety-seven independent single nucleotide polymorphisms (SNPs) are robustly associated with adult body mass index (BMI kg/m〈sup〉2〈/sup〉) in Caucasian populations. The relevance of such variants in African populations at different stages of the life course (such as childhood) is unclear. We tested whether a genetic risk score composed of the aforementioned SNPs was associated with BMI from infancy to early adulthood. We further tested whether this genetic effect was mediated by conditional weight gain at different growth periods. We used data from the Birth to Twenty Plus Cohort (Bt20+), for 971 urban South African black children from birth to 18 years. DNA was collected at 13 years old and was genotyped using the Metabochip (Illumina) array. The weighted genetic risk score (wGRS) for BMI was constructed based on 71 of the 97 previously reported SNPs.〈/p〉 〈/span〉 〈span〉 〈h3〉Results〈/h3〉 〈p〉The cross-sectional association between the wGRS and BMI strengthened with age from 5 to 18 years. The significant associations were observed from 11 to 18 years, and peak effect sizes were observed at 13 and 14 years of age. Results from the linear mixed effects models showed significant interactions between the wGRS and age on longitudinal BMI but no such interactions were observed in sex and the wGRS. A higher wGRS was associated with an increased relative risk of belonging to the early onset obese longitudinal BMI trajectory (relative risk = 1.88; 95%CI 1.28 to 2.76) compared to belonging to a normal longitudinal BMI trajectory. Adolescent conditional relative weight gain had a suggestive mediation effect of 56% on the association between wGRS and obesity risk at 18 years.〈/p〉 〈/span〉 〈span〉 〈h3〉Conclusions〈/h3〉 〈p〉The results suggest that genetic susceptibility to higher adult BMI can be tracked from childhood in this African population. This supports the notion that prevention of adult obesity should begin early in life. The genetic risk score combined with other non-genetic risk factors, such as BMI trajectory membership in our case, has the potential to be used to screen for early identification of individuals at increased risk of obesity and other related NCD risk factors in order to reduce the adverse health risk outcomes later.〈/p〉 〈/span〉

Description: 〈h3〉Abstract〈/h3〉 〈span〉 〈h3〉Background〈/h3〉 〈p〉The neurodegenerative disorder Alzheimer’s disease is caused by the accumulation of toxic aggregates of β-amyloid in the human brain. On the one hand, hyperhomocysteinemia has been shown to be a risk factor for cognitive decline in Alzheimer’s disease. On the other hand, betaine has been demonstrated to attenuate Alzheimer-like pathological changes induced by homocysteine. It is reasonable to conclude that this is due to triggering the remethylation pathway mediated by betaine-homocysteine-methyltransferase. In the present study, we used the transgenic 〈em〉Caenorhabditis elegans〈/em〉 strain CL2006, to test whether betaine is able to reduce β-amyloid-induced paralysis in 〈em〉C. elegans〈/em〉. This model expresses human β-amyloid 1–42 under control of a muscle-specific promoter that leads to progressive, age-dependent paralysis in the nematodes.〈/p〉 〈/span〉 〈span〉 〈h3〉Results〈/h3〉 〈p〉Betaine at a concentration of 100 μM was able to reduce homocysteine levels in the presence and absence of 1 mM homocysteine. Simultaneously, betaine both reduced normal paralysis rates in the absence of homocysteine and increased paralysis rates triggered by addition of homocysteine. Knockdown of cystathionine-β-synthase using RNA interference both increased homocysteine levels and paralysis. Additionally, it prevented the reducing effects of betaine on homocysteine levels and paralysis.〈/p〉 〈/span〉 〈span〉 〈h3〉Conclusion〈/h3〉 〈p〉Our studies show that betaine is able to reduce homocysteine levels and β-amyloid-induced toxicity in a 〈em〉C. elegans〈/em〉 model for Alzheimer’s disease. This effect is independent of the remethylation pathway but requires the transsulfuration pathway mediated by cystathionine-β-synthase.〈/p〉 〈/span〉

Description: 〈h3〉Abstract〈/h3〉 〈span〉 〈h3〉Background〈/h3〉 〈p〉Intrauterine growth-restricted (IUGR) neonates impair postnatal skeletal muscle growth. The aim of this study was to investigate whether high nutrient intake (HNI) during the suckling period could improve muscle growth and metabolic status of IUGR pigs.〈/p〉 〈/span〉 〈span〉 〈h3〉Methods〈/h3〉 〈p〉Twelve pairs of IUGR and normal birth weight (NBW) pigs (7 days old) were randomly assigned to adequate nutrient intake and HNI formula milk groups. Psoas major (PM) muscle sample was obtained after 21 days of rearing.〈/p〉 〈/span〉 〈span〉 〈h3〉Results〈/h3〉 〈p〉IUGR decreased cross-sectional areas (CSA) and myofiber numbers, activity of lactate dehydrogenase (LDH), and mRNA expression of insulin-like growth factor 1 (IGF-1), IGF-1 receptor (IGF-1R), mammalian target of rapamycin (mTOR), ribosomal protein s6 (RPS6), eukaryotic translation initiation factor 4E (eIF4E), protein expression of phosphorylated mTOR (P-mTOR), and phosphorylated protein kinase B (P-Akt) in the PM muscle of pigs. Irrespective of birth weight, HNI increased muscle weight and CSA, the concentration of RNA, and ratio of RNA to DNA, as well as ratio of LDH to β-hydroxy-acyl-CoA-dehydrogenase in the PM muscle of pigs. Furthermore, HNI increased percentages of MyHC IIb, mRNA expression of IGF-1, IGF-1R, Akt, mTOR, RPS6, and eIF4E, as well as protein expression of P-mTOR, P-Akt, P-RPS6, and P-eIF4E in the PM muscle of pigs.〈/p〉 〈/span〉 〈span〉 〈h3〉Conclusion〈/h3〉 〈p〉The present findings suggest that high nutrient intake during the suckling period could improve skeletal muscle growth and maturity, which is associated with increasing the expression of protein deposition-related genes and accelerating the development of glycolytic-type myofiber in pigs.〈/p〉 〈/span〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉The suitability of 〈em〉C. elegans〈/em〉 as a model for the question of nutritional science is a controversial topic. The discussion makes clear that 〈em〉C. elegans〈/em〉 is its own best model for revealing, via genetic approaches, biological principles of nutritional behavior, and the biochemical function of vitamins. In this case, the model has a discovery function. Worm research serves also in the identification of nutrition-dependent pathways that could be used for novel approaches in human nutritional studies. This heuristic function of the model guides the applied nutrition research in an innovative direction. Since the nutrition and metabolism for the worm and man differ from each other somewhat strongly, results of nutritional studies in 〈em〉C. elegans〈/em〉 are not directly applicable to human nutrition. In general, the 〈em〉C. elegans〈/em〉 model is primarily appropriate for explaining the causality of general species’ nutritional phenotypes. Experience tells us that the analysis of drastic nutritional phenotypes in 〈em〉C. elegans〈/em〉 has the potential to enrich the canon of knowledge of nutritional science.〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈span〉 〈h3〉Background〈/h3〉 〈p〉There is increasing evidence indicating an aberrant expression of miRNAs in colorectal cancer (CRC) development. Growing evidence has suggested that polyunsaturated fatty acids (PUFAs) could modulate the remodeling of the epigenome. No study has yet been published to examine the direct effect of PUFA on the promoter methylation of miRNAs. This study aimed to examine the potential clinical application of PUFA on the promoter DNA methylation of miR-126 and its angiogenic target molecule (VEGF) in the CRC cells.〈/p〉 〈/span〉 〈span〉 〈h3〉Methods〈/h3〉 〈p〉We investigated the direct effect of 100 μM EPA, DHA, and LA for 24 h on promoter methylation status of miR-126 in a panel of five CRC cell lines (HCT116, HT29/219, Caco2, SW742, and LS180) by methylation-specific PCR (MSP). We also quantified the miR-126 and VEGF transcript expression levels in five CRC cell lines affected by PUFA by real-time PCR. Moreover, we analyzed the protein expression level of VEGF, as a target of miR-126, by western blotting assay.〈/p〉 〈/span〉 〈span〉 〈h3〉Results〈/h3〉 〈p〉MSP analysis showed extensive DNA methylation of the miR-126 promoter in all five CRC cell lines, and among all three PUFAs, only DHA completely demethylated the promoter of miR-126 in HCT116 and Caco2 cell lines. We found that only DHA significantly induces the expression level of miR-126 in HCT116 and Caco2 cell lines, respectively, by 20.1-fold and 1.68-fold (〈em〉p〈/em〉 〈 0.05). Our finding indicates that the downregulation of VEGF protein level is also effectively observed only in DHA-treated HCT116 and Caco2 cells compared to control cells (〈em〉p〈/em〉 〈 0.05).〈/p〉 〈/span〉 〈span〉 〈h3〉Conclusions〈/h3〉 〈p〉Our results provide evidence that 〈em〉n〈/em〉-3 PUFAs are able to modulate cellular miR-126 DNA methylation and inhibit VEGF expression level in a cell-type specific manner in colorectal cancer cells. DHA always showed higher efficacy than EPA and LA in our experiment. Overall, our results suggest a potential clinical application of 〈em〉n〈/em〉-3 PUFAs as anti-angiogenic agents in CRC therapy.〈/p〉 〈/span〉

Description: 〈h3〉Abstract〈/h3〉 〈span〉 〈h3〉Background〈/h3〉 〈p〉Several muscle-specific microRNAs (myomiRs) are differentially expressed during cellular senescence. However, the role of dietary compounds on myomiRs remains elusive. This study aimed to elucidate the modulatory role of tocotrienol-rich fraction (TRF) on myomiRs and myogenic genes during differentiation of human myoblasts. Young and senescent human skeletal muscle myoblasts (HSMM) were treated with 50 μg/mL TRF for 24 h before and after inducing differentiation.〈/p〉 〈/span〉 〈span〉 〈h3〉Results〈/h3〉 〈p〉The fusion index and myotube surface area were higher (〈em〉p〈/em〉 〈 0.05) on days 3 and 5 than that on day 1 of differentiation. Ageing reduced the differentiation rate, as observed by a decrease in both fusion index and myotube surface area in senescent cells (〈em〉p〈/em〉 〈 0.05). Treatment with TRF significantly increased differentiation at days 1, 3 and 5 of young and senescent myoblasts. In senescent myoblasts, TRF increased the expression of 〈em〉miR-206〈/em〉 and 〈em〉miR-486〈/em〉 and decreased 〈em〉PTEN〈/em〉 and 〈em〉PAX7〈/em〉 expression〈em〉.〈/em〉 However, the expression of 〈em〉IGF1R〈/em〉 was upregulated during early differentiation and decreased at late differentiation when treated with TRF. In young myoblasts, TRF promoted differentiation by modulating the expression of 〈em〉miR-206〈/em〉, which resulted in the reduction of 〈em〉PAX7〈/em〉 expression and upregulation of 〈em〉IGF1R〈/em〉.〈/p〉 〈/span〉 〈span〉 〈h3〉Conclusion〈/h3〉 〈p〉TRF can potentially promote myoblast differentiation by modulating the expression of myomiRs, which regulate the expression of myogenic genes.〈/p〉 〈/span〉

Description: 〈h3〉Abstract〈/h3〉 〈span〉 〈h3〉Background〈/h3〉 〈p〉Energy homeostasis is regulated by the hypothalamus but fails when animals are fed a high-fat diet (HFD), and leptin insensitivity and obesity develops. To elucidate the possible mechanisms underlying these effects, a microarray-based transcriptomics approach was used to identify novel genes regulated by HFD and leptin in the mouse hypothalamus.〈/p〉 〈/span〉 〈span〉 〈h3〉Results〈/h3〉 〈p〉Mouse global array data identified 〈em〉serpinA3N〈/em〉 as a novel gene highly upregulated by both a HFD and leptin challenge. In situ hybridisation showed 〈em〉serpinA3N〈/em〉 expression upregulation by HFD and leptin in all major hypothalamic nuclei in agreement with transcriptomic gene expression data. Immunohistochemistry and studies in the hypothalamic clonal neuronal cell line, mHypoE-N42 (N42), confirmed that alpha 1-antichymotrypsin (α〈sub〉1〈/sub〉AC), the protein encoded by 〈em〉serpinA3〈/em〉, is localised to neurons and revealed that it is secreted into the media. 〈em〉SerpinA3N〈/em〉 expression in N42 neurons is upregulated by palmitic acid and by leptin, together with 〈em〉IL-6〈/em〉 and 〈em〉TNFα〈/em〉, and all three genes are downregulated by the anti-inflammatory monounsaturated fat, oleic acid. Additionally, palmitate upregulation of 〈em〉serpinA3〈/em〉 in N42 neurons is blocked by the NFκB inhibitor, BAY11, and the upregulation of 〈em〉serpinA3N〈/em〉 expression in the hypothalamus by HFD is blunted in IL-1 receptor 1 knockout (〈em〉IL-1R1〈/em〉〈sup〉〈em〉−/−〈/em〉〈/sup〉) mice.〈/p〉 〈/span〉 〈span〉 〈h3〉Conclusions〈/h3〉 〈p〉These data demonstrate that 〈em〉serpinA3〈/em〉 expression is implicated in nutritionally mediated hypothalamic inflammation.〈/p〉 〈/span〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉There is a growing interest in assessing dietary intake more accurately across different population groups, and biomarkers have emerged as a complementary tool to replace traditional dietary assessment methods. The purpose of this study was to conduct a systematic review of the literature available and evaluate the applicability and validity of biomarkers of legume intake reported across various observational and intervention studies. A systematic search in PubMed, Scopus, and ISI Web of Knowledge identified 44 studies which met the inclusion criteria for the review. Results from observational studies focused on soy or soy-based foods and demonstrated positive correlations between soy intake and urinary, plasma or serum isoflavonoid levels in different population groups. Similarly, intervention studies demonstrated increased genistein and daidzein levels in urine and plasma following soy intake. Both genistein and daidzein exhibited dose-response relationships. Other isoflavonoid levels such as 〈em〉O〈/em〉-desmethylangolensin (〈em〉O〈/em〉-DMA) and equol were also reported to increase following soy consumption. Using a developed scoring system, genistein and daidzein can be considered as promising candidate markers for soy consumption. Furthermore, genistein and daidzein also served as good estimates of soy intake as evidenced from long-term exposure studies marking their status as validated biomarkers. On the contrary, only few studies indicated proposed biomarkers for pulses intake, with pipecolic acid and 〈em〉S〈/em〉-methylcysteine reported as markers reflecting dry bean consumption, unsaturated aliphatic, hydroxyl-dicarboxylic acid related to green beans intake and trigonelline reported as marker of peas consumption. However, data regarding criteria such as specificity, dose-response and time-response relationship, reliability, and feasibility to evaluate the validity of these markers is lacking. In conclusion, despite many studies suggesting proposed biomarkers for soy, there is a lack of information on markers of other different subtypes of legumes. Further discovery and validation studies are needed in order to identify reliable biomarkers of legume intake.〈/p〉

Description: Nutritional therapy is well established as a means to induce remission in active Crohn’s disease (CD). Evidence indicates that exclusive enteral nutrition (EEN) therapy for CD both alters the intestinal microbiota and directly suppresses the inflammatory response in the intestinal mucosa. However, the pathway(s) through which EEN suppresses inflammation is still unknown. Therefore, the aim of the current study was to use microarray technology to investigate the major pathway by which polymeric formula (PF) alters inflammatory processes in epithelial cells in vitro. HT-29 cells were grown to confluence and then co-cultured with tumour necrosis factor (TNF)-α (100 ng/ml) for 5 h in the presence or absence of PF, as used for EEN. Following incubation, RNA was extracted and subjected to polymerase chain reaction (PCR) and microarray analysis. Enzyme-linked immunosorbent assays were employed to evaluate cytokine protein levels. Neither TNF-α nor PF had a toxic effect on cells over the experimental period. Microarray analysis showed that PF modulated the expression of genes specifically linked to nuclear factor (NF)-κB, resulting in downregulation of a number of genes in this pathway. These findings were further confirmed by real-time PCR of selected dysregulated genes as well as reduced expression of IL-6 and IL-8 proteins following PF treatment. The results arising from this study provide evidence that PF alters the inflammatory responses in intestinal epithelial cells through modulation of the NF-κB pathway.

Description: Several dietary agents, such as micronutrient and non-nutrient components, the so-called bioactive food components, have been shown to display anticancer properties and influence genetic processes. The most common epigenetic change is DNA methylation. Hypomethylation of long interspersed elements (LINE-1) has been associated with an increased risk of several cancers, although conflicting findings have also been observed. The aim of the present study was to test the hypothesis that a low adherence to the Mediterranean diet (MD) and folate deficiency may cause LINE-1 hypomethylation in blood leukocytes of healthy women, and thus genomic instability. One hundred and seventy-seven non-pregnant women were enrolled. Mediterranean diet score (MDS) and folate intake were calculated using a food frequency questionnaire. LINE-1 methylation level was measured by pyrosequencing analysis in three CpG sites of LINE-1 promoter. According to MDS, only 9.6 % of subjects achieved a high adherence to MD. Taking into account the use of supplements, there was a high prevalence of folate deficiency (73.4 %). Women whose consumption of fruit was below the median value (i.e., 〈201 gr/day) were 3.7 times more likely to display LINE-1 hypomethylation than women whose consumption was above the median value (OR 3.7; 95 % CI 1.4–9.5). Similarly, women with folate deficiency were 3.6 times more likely to display LINE-1 hypomethylation than women with no folate deficiency (OR 3.6; 95 % CI 1.1–12.1). A dietary pattern characterized by low fruit consumption and folate deficiency is associated with LINE-1 hypomethylation and with cancer risk.

Description: The inhibitory neurotransmitter GABA (γ-aminobutyric acid) is synthesized by glutamic acid decarboxylase, which is expressed in the central nervous system and in various other tissues including the intestine. Moreover, GABA can be ingested in vegetarian diets or produced by bacterial commensals in the gastrointestinal tract. As previous studies in lung have suggested a link between locally increased GABA availability and mucin 5AC production, the present study sought to test whether the presence or lack of GABA (and its precursor glutamine) has an effect on intestinal mucin expression. Porcine jejunum epithelial preparations were incubated with two different amounts of GABA or glutamine on the mucosal side for 4 h, and changes in the relative gene expression of seven different mucins, enzymes involved in mucin shedding, GABA B receptor, enzymes involved in glutamine/GABA metabolism, glutathione peroxidase 2, and interleukin 10 were examined by quantitative PCR (TaqMan ® assays). Protein expression of mucin-1 (MUC1) was analyzed by Western blot. On the RNA level, only MUC1 was significantly up-regulated by both GABA concentrations compared with the control. Glutamine-treated groups showed the same trend. On the protein level, all treatment groups showed a significantly higher MUC1 expression than the control group. We conclude that GABA selectively increases the expression of MUC1, a cell surface mucin that prevents the adhesion of microorganisms, because of its size and negative charge, and therefore propose that the well-described positive effects of glutamine on enterocytes and intestinal integrity are partly attributable to effects of its metabolite GABA.

Description: The hypothalamus integrates energy balance information from the periphery using different neuronal subtypes within each of the hypothalamic areas. However, the effects of prandial state on global mRNA, microRNA and long noncoding (lnc) RNA expression within the whole hypothalamus are largely unknown. In this study, mice were given either a 24-h fast, or ad libitum access to food. RNA samples were analyzed by microarray, and then a subset was confirmed using quantitative real-time PCR (QPCR). A total of 540 mRNAs were either up- or down-regulated with food deprivation. Since gene ontology enrichment analyses identified several categories of mRNAs related to cell cycle processes, ten cell-cycle-related genes were further analyzed using QPCR with six confirmed to be significantly up-regulated and one down-regulated in response to 24-h fasting. While 22 independent microRNAs were differentially expressed by microarray, secondary analysis by QPCR failed to confirm significant changes with fasting. There were 622 lncRNAs identified as differentially expressed, and of three tested by QPCR, two were confirmed. Overall, this is the first time that expression of hypothalamic lncRNAs has been shown to be responsive to food deprivation. In addition, this study is the first to identify a list of lncRNAs with high expression in RNA extracted from hypothalamus. Individual contributions from specific miRNA, lncRNA and mRNAs to the food deprivation response can now be further studied at the physiological and biochemical levels.

Description: Food components with anti-obesity properties are commonly evaluated using mouse models of diet-induced obesity. The ability of these components to reduce or prevent white adipose tissue (WAT) accumulation is usually tested in feeding trials of several weeks duration in order to detect significant effects on fat mass expansion. Here, we aimed to identify early, predictive biomarkers for WAT expansion. We performed a 5-day high-fat diet (HFD) feeding trial with C57BL/6J mice using different established anti-obesity interventions: epigallocatechin gallate, replacing dietary lipids by n-3 PUFA, and increasing dietary protein. WAT gene expression was analyzed of genes known to be similarly affected by short- and long-term HFD. Gene expression of Leptin and Mest (mesoderm-specific transcript) was increased by HFD and normalized by all anti-obesity interventions. In a second experiment, translatability to whole blood-based expression data was assessed. Mice were challenged for 21 days with a HFD without or with simultaneous treatment with anti-obesity bioactives, hydroxytyrosol or resveratrol, and compared for parameters including Leptin and Mest expression in whole blood at day 5. While Leptin mRNA could not be detected in mouse whole blood, there was an induction of Mest mRNA by HFD which was suppressed by hydroxytyrosol. Moreover, Mest expression in whole blood at day 5 positively correlated with adiposity and negatively with lean body mass and the subcutaneous/visceral fat ratio at day 21. We conclude that gene expression of Leptin and Mest in WAT and of Mest in whole blood represent early, predictive markers of adipose tissue expansion of potential usefulness in nutritional studies and trials.

Description: Obesity is associated with chronic diseases such as fatty liver, type 2 diabetes, cardiovascular disease, and severe metabolic syndrome. Obesity causes metabolic impairment including excessive lipid accumulation and fibrosis in the hepatic tissue as well as the increase in oxidative stress. In order to investigate the effect of mulberry leaf ( Morus alba L.) extract (MLE) on obesity-induced oxidative stress, lipogenesis, and fibrosis in liver, MLE has been gavaged for 12 weeks in high-fat diet (HFD)-induced obese mice. MLE treatment significantly ameliorated LXRα-mediated lipogenesis and hepatic fibrosis markers such as α-smooth muscle actin, while MLE up-regulated lipolysis-associated markers such as lipoprotein lipase in the HFD-fed mice. Moreover, MLE normalized the activities of antioxidant enzymes including heme oxygenase-1 and glutathione peroxidase in accordance with protein levels of 4-hydroxynonenal in the HFD-fed mice. MLE has beneficial effects on obesity-related fatty liver disease by regulation of hepatic lipid metabolism, fibrosis, and antioxidant defense system. MLE supplementation might be a potential therapeutic approach for obesity-related disease including non-alcoholic fatty liver disease.

Description: Background Marine long-chain polyunsaturated fatty acids are susceptible to oxidation, generating a range of different oxidation products with suggested negative health effects. The aim of the present study was to utilize sensitive high-throughput transcriptome analyses to investigate potential unfavorable effects of oxidized fish oil (PV: 18 meq/kg; AV: 9) compared to high-quality fish oil (PV: 4 meq/kg; AV: 3). Methods In a double-blinded randomized controlled study for seven weeks, 35 healthy subjects were assigned to 8 g of either oxidized fish oil or high quality fish oil. The daily dose of EPA+DHA was 1.6 g. Peripheral blood mononuclear cells were isolated at baseline and after 7 weeks and transcriptome analyses were performed with the illuminaHT-12 v4 Expression BeadChip. Results No gene transcripts, biological processes, pathway or network were significantly changed in the oxidized fish oil group compared to the fish oil group. Furthermore, gene sets related to oxidative stress and cardiovascular disease were not differently regulated between the groups. Within group analyses revealed a more prominent effect after intake of high quality fish oil as 11 gene transcripts were significantly (FDR 〈 0.1) changed from baseline versus three within the oxidized fish oil group. Conclusion The suggested concern linking lipid oxidation products to short-term unfavorable health effects may therefore not be evident at a molecular level in this explorative study. Trial registration ClinicalTrials.gov, NCT01034423

Description: Background The mechanism of db-cAMP regulating fat deposition and improving lean percentage is unclear and needs to be further studied. Methods Eighteen 100-day-old Duroc × Landrance × Large White barrows (49.75 ± 0.75 kg) were used for experiment 1, and 15 eighteen 135-day-old barrows (78.34 ± 1.22 kg) were used for experiment 2 to investigate the effects of dietary dibutyryl-cAMP (db-cAMP) on fat deposition in finishing pigs. Pigs were fed with a corn-soybean meal-based diet supplemented with 0 or 15 mg/kg db-cAMP, and both experiments lasted 35 days, respectively. Results The results showed that db-cAMP decreased the backfat thickness, backfat percentage, and diameter of backfat cells without changing the growth performance or carcass characteristics in both experiments, and this effect was more marked in experiment 1 than in experiment 2; db-cAMP enhanced the activity of the growth hormone–insulin-like growth factor-1 (GH-IGF-1) axis and pro-opiomelanocortin (POMC) system in both experiments, which suppressed the accumulation of backfat deposition; microarray analysis showed that db-cAMP suppressed the inflammatory system within the adipose tissue related to insulin sensitivity, which also reduced fat synthesis. Conclusions In summary, the effect of db-cAMP on suppressing fat synthesis and accumulation is better in the earlier phase than in the later phase of finishing pigs, and db-cAMP plays this function by increasing the activity of the GH-IGF-1 axis and POMC system, while decreasing the inflammatory system within the adipose tissue related to insulin sensitive or lipolysis.

Description: Background By taking diet quality into account, we may clarify the relationship between genetically elevated triglycerides (TG) and low-density lipoprotein-cholesterol (LDL-C), and better understand the inconsistent results regarding genetically elevated high-density lipoprotein-cholesterol (HDL-C), and cardiovascular disease (CVD) risk. Methods We included 24,799 participants (62 % women, age 44–74 years) from the Malmö Diet and Cancer cohort. During a mean follow-up time of 15 years, 3068 incident CVD cases (1814 coronary and 1254 ischemic stroke) were identified. Genetic risk scores (GRSs) were constructed by combining 80 validated genetic variants associated with higher TG and LDL-C or lower HDL-C. The participants’ dietary intake, assessed by a modified diet history method, was ranked according to a diet quality index that included six dietary components: saturated fat, polyunsaturated fat, fish, fiber, fruit and vegetables, and sucrose. Results The GRS LDL-C ( P  = 5 × 10 −6 ) and GRS HDL-C ( P  = 0.02) but not GRS TG ( P  = 0.08) were significantly associated with CVD risk. No significant interaction between the GRSs and diet quality was observed on CVD risk ( P  〉 0.39). A high compared to a low diet quality attenuated the association between GRS LDL-C and the risk of incident ischemic stroke ( P interaction = 0.01). Conclusion We found some evidence of an interaction between diet quality and GRS LDL-C on ischemic stroke.

Description: To study host–probiotic interactions in parts of the intestine only accessible in humans by surgery (jejunum, ileum and colon), pigs were used as model for humans. Groups of eight 6-week-old pigs were repeatedly orally administered with 5 × 10 12 CFU Lactobacillus plantarum 299v ( L. plantarum 299v) or PBS, starting with a single dose followed by three consecutive daily dosings 10 days later. Gene expression was assessed with pooled RNA samples isolated from jejunum, ileum and colon scrapings of the eight pigs per group using Affymetrix porcine microarrays. Comparison of gene expression profiles recorded from L. plantarum 299v-treated pigs with PBS-treated pigs indicated that L. plantarum 299v affected metabolic and immunological processes, particularly in the ileum. A higher expression level of several B cell-specific transcription factors/regulators was observed, suggesting that an influx of B cells from the periphery to the ileum and/or the proliferation of progenitor B cells to IgA-committed plasma cells in the Peyer’s patches of the ileum was stimulated. Genes coding for enzymes that metabolize leukotriene B4, 1,25-dihydroxyvitamin D3 and steroids were regulated in the ileum. Bioinformatics analysis predicted that these metabolites may play a role in the crosstalk between intestinal immune cells and sub-mucosal adipocytes. Together with regulation of genes that repress NFKB- and PPARG-mediated transcription, this crosstalk may contribute to tempering of inflammatory reactions. Furthermore, the enzyme adenosine deaminase, responsible for the breakdown of the anti-inflammatory mediator adenosine, was strongly down-regulated in response to L. plantarum 299v. This suggested that L. plantarum 299v-regulated production of adenosine by immune cells like regulatory T cells may also be a mechanism that tempers inflammation in the ileum, and perhaps also in other parts of the pig’s body.

Description: Inflammation is a critical contributor to the pathogenesis of metabolic disorders with adipose tissue being crucial in the inflammatory response by releasing multiple adipokines with either pro- or anti-inflammatory activities with potential functions as metabolic regulators. Peripheral blood mononuclear cells (PBMC) have been proposed as representative of the inflammatory status in obesity. The aim of the present study was to evaluate the contribution of PBMC to the obesity-associated chronic inflammation analyzing the expression of novel adipokines. Samples obtained from 69 subjects were used in the study. Real-time PCR determinations were performed to quantify gene expression levels in PBMC of novel adipokines including chemerin, chitinase-3-like protein 1 (YKL-40), lipocalin-2 (LCN-2) and osteopontin (OPN), and their circulating concentrations were also determined by ELISA. We show, for the first time, that PBMC gene expression levels of chemerin ( P  〈 0.0001), chitinase-3-like protein 1 ( P  = 0.010), lipocalin-2 ( P  〈 0.0001) and osteopontin ( P  〈 0.0001) were strongly upregulated in obesity independently of the glycemic state. Circulating concentrations of these adipokines followed the same trend being significantly higher ( P  〈 0.05) in obese normoglycemic and type 2 diabetic patients compared to lean volunteers and also associated ( P  〈 0.05) with their corresponding mRNA levels in PBMC. These results provide evidence that alterations in inflammation-related adipokines are manifest in PBMC, which might contribute to the low-grade chronic inflammation that characterizes obesity.

Description: Nutrition research is struggling to demonstrate beneficial health effects, since nutritional effects are often subtle and long term. Health has been redefined as the ability of our body to cope with daily-life challenges. Physiology acts as a well-orchestrated machinery to adapt to the continuously changing environment. We term this adaptive capacity “phenotypic flexibility.” The phenotypic flexibility concept implies that health can be measured by the ability to adapt to conditions of temporary stress, such as physical exercise, infections or mental stress, in a healthy manner. This may offer a more sensitive way to assess changes in health status of healthy subjects. Here, we performed a systematic review of 61 studies applying different nutritional stress tests to quantify health and nutritional health effects, with the objective to define an optimal nutritional stress test that has the potential to be adopted as the golden standard in nutrition research. To acknowledge the multi-target role of nutrition, a relevant subset of 50 processes that govern optimal health, with high relevance to diet, was used to define phenotypic flexibility. Subsequently, we assessed the response of biomarkers related to this subset of processes to the different challenge tests. Based on the obtained insights, we propose a nutritional stress test composed of a high-fat, high-caloric drink, containing 60 g palm olein, 75 g glucose and 20 g dairy protein in a total volume of 400 ml. The use of such a standardized nutritional challenge test in intervention studies is expected to demonstrate subtle improvements of phenotypic flexibility, thereby enabling substantiation of nutritional health effects.

Description: Recently, a great deal of interest has been expressed regarding strategies to tackle worldwide obesity because of its accelerated wide spread accompanied with numerous negative effects on health and high costs. Obesity has been traditionally associated with an imbalance in energy consumed when compared to energy expenditure. However, growing evidence suggests a less simplistic event in which gut microbiota plays a key role. Obesity, in terms of microbiota, is a complicated disequilibrium that presents many unclear complications. Despite this, there is special interest in characterizing compositionally and functionally the obese gut microbiota with the help of in vitro, animal and human studies. Considering the gut microbiota as a factor contributing to human obesity represents a tool of great therapeutic potential. This paper reviews the use of antimicrobials, probiotics, fecal microbial therapy, prebiotics and diet to manipulate obesity through the human gut microbiota and reveals inconsistencies and implications for future study.

Description: Consuming a high-fat/high-fructose diet (HFD) starting at a young age leads to the development of obesity and to the progression of metabolic syndrome (MS). We are interested in the relationship between MS and DNA methylation as a mediator of the metabolic memory and the early appearance of these diseases in the progeny. To this end, Wistar rats were fed a HFD for 1 year, and every 12 weeks, biochemical analyses were performed. After 24 weeks, animals fed the HFD showed alterations related to MS such as elevated blood levels of fasting glucose, triglycerides, and insulin compared with their littermate controls. During the experimental period, the control females exhibited a 40 % lower 5-methylcytosine (5-mC) level compared to the control males. The HFD affected the 5-mC levels in males and females differently. The HFD induced a 20 % decrease in the 5-mC levels in males and a 15 % increase in females. We found that the HFD induces an early presentation of MS in the progeny of treated animals and that the DNA methylation was altered in the F 1 generation. The presentation of MS is positively associated with changes in the global percentage of 5-mC in the DNA.

Description: Health is influenced by interplay of molecular, physiological and environmental factors. To effectively maintain health and prevent disease, health-relevant relations need to be understood at multiple levels of biological complexity. Network-based methods provide a powerful platform for integration and mining of data and knowledge characterizing different aspects of health. Previously, we have reported physiological and gene expression changes associated with adaptation of murine epididymal white adipose tissue (eWAT) to 5 days and 12 weeks of high-fat diet (HFD) and low-fat diet feeding (Voigt et al. in Mol Nutr Food Res 57:1423–1434, 2013 . doi: 10.1002/mnfr.201200671 ). In the current study, we apply network analysis on this dataset to comprehensively characterize mechanisms driving the short- and long-term adaptation of eWAT to HFD across multiple levels of complexity. We built a three-layered interaction network comprising enriched biological processes, their transcriptional regulators and associated changes in physiological parameters. The multi-layered network model reveals that early eWAT adaptation to HFD feeding involves major changes at a molecular level, including activation of TGF-β signalling pathway, immune and stress response and downregulation of mitochondrial functioning. Upon prolonged HFD intake, initial transcriptional response tails off, mitochondrial functioning is even further diminished, and in turn the relation between eWAT gene expression and physiological changes becomes more prominent. In particular, eWAT weight and total energy intake negatively correlate with cellular respiration process, revealing mitochondrial dysfunction as a hallmark of late eWAT adaptation to HFD. Apart from global understanding of the time-resolved adaptation to HFD, the multi-layered network model allows several novel mechanistic hypotheses to emerge: (1) early activation of TGF-β signalling as a trigger for structural and morphological changes in mitochondrial organization in eWAT, (2) modulation of cellular respiration as an intervention strategy to effectively deal with excess dietary fat and (3) discovery of putative intervention targets, such those in pathways related to appetite control. In conclusion, the generated network model comprehensively characterizes eWAT adaptation to high-fat diet, spanning from global aspects to mechanistic details. Being open to further exploration by the research community, it provides a resource of health-relevant interactions ready to be used in a broad range of research applications.

Description: Iron-deficient anemia is a prevalent disease among humans. We searched for genes regulated by iron deficiency and its regulated mechanism. cDNA microarrays were performed using Hepa1c1c7 cells treated with 100 μM desferrioxamine (DFO), an iron chelator. Early growth response 1 (Egr1) was upregulated with at least 20-fold increase within 4 h and lasted for 24 h, which was confirmed by qRT-PCR. This activation was not seen by ferric ammonium citrate (FAC). DFO increased the transcriptional activity of Egr1-luc (−604 to +160) and serum response element (SRE)-luc reporters by 2.7-folds. In addition, cycloheximide lowered DFO-induced Egr1 mRNA levels. The upregulation of Egr1 by DFO was accompanied by sustained ERK signals along with phosphorylation of Elk-1. The ERK inhibitor (PD98059) prevented the DFO-induced Egr1 mRNAs. Overexpression of Elk-1 mutant (pElk-1S383A) decreased Egr1 reporter activity. DFO lowered reactive oxygen species (ROS) production and increased caspase 3/7 activity and cell death. DFO-induced iron deficiency upregulates Egr1 in part through transcriptional activation via ERK and Elk-1 signals, which may be important in the regulation of cell death in hepatoma cells. Our study demonstrated that iron depletion controlled the expression of Egr1, which might contribute to decisions about cellular fate in response to iron deficiency.

Description: Healthy nutrition is accepted as a cornerstone of public health strategies for reducing the risk of noncommunicable conditions such as obesity, cardiovascular disease, and related morbidities. However, many research studies continue to focus on single or at most a few factors that may elicit a metabolic effect. These reductionist approaches resulted in: (1) exaggerated claims for nutrition as a cure or prevention of disease; (2) the wide use of empirically based dietary regimens, as if one fits all; and (3) frequent disappointment of consumers, patients, and healthcare providers about the real impact nutrition can make on medicine and health. Multiple factors including environment, host and microbiome genetics, social context, the chemical form of the nutrient, its (bio)availability, and chemical and metabolic interactions among nutrients all interact to result in nutrient requirement and in health outcomes. Advances in laboratory methodologies, especially in analytical and separation techniques, are making the chemical dissection of foods and their availability in physiological tissues possible in an unprecedented manner. These omics technologies have opened opportunities for extending knowledge of micronutrients and of their metabolic and endocrine roles. While these technologies are crucial, more holistic approaches to the analysis of physiology and environment, novel experimental designs, and more sophisticated computational methods are needed to advance our understanding of how nutrition influences health of individuals.

Description: Iron homeostasis in the human body is maintained primarily through regulation of iron absorption in the duodenum. The liver peptide hepcidin plays a central role in this regulation. Additionally, expression and functional control of certain components of the cellular iron transport machinery can be influenced directly by the iron status of enterocytes. The significance of this modulation, relative to the effects of hepcidin, and the comparative effects of iron obtained directly from the diet and/or via the bloodstream are not clear. The studies described here were performed using Caco-2 cell monolayers as a model of intestinal epithelium, to compare the effects of iron supplied in physiologically relevant forms to either the apical or basolateral surfaces of the cells. Both sources of iron provoked increased cellular ferritin content, indicating iron uptake from both sides of the cells. Supply of basolateral transferrin-bound iron did not affect subsequent iron transport across the apical surface, but reduced iron transport across the basolateral membrane. In contrast, the apical iron supply led to subsequent reduction in iron transport across the apical cell membrane without altering iron export across the basolateral membrane. The apical and basolateral iron supplies also elicited distinct effects on the expression and subcellular distribution of iron transporters. These data suggest that, in addition to the effects of cellular iron status on the expression of iron transporter genes, different modes and direction of iron supply to enterocytes can elicit distinct functional effects on iron transport.

Description: Recent studies have established the interaction between APOA2 −256T〉C polymorphism and dietary saturated fatty acids intake in relation to obesity on healthy individuals. In the current study, we investigate the effects of this interaction on anthropometric variables and serum levels of leptin and ghrelin in patients with type 2 diabetes. In this cross-sectional study, 737 patients with type 2 diabetes mellitus (290 males and 447 females) were recruited from diabetes clinics in Tehran. The usual dietary intake of all participants during the last year was obtained by validated semiquantitative food frequency questionnaire. APOA2 genotyping was performed by real-time PCR on genomic DNA. No significant relation was obtained by univariate analysis between anthropometric variables and APOA2 genotypes. However, after adjusting for age, gender, physical activity and total energy intake, we identified a significant interaction between APOA2 -saturated fatty acids intake and body mass index (BMI). After adjusting for potential confounders, serum levels of ghrelin in CC genotype patients were significantly higher than T allele carriers ( p  = 0.03), whereas the case with leptin did not reveal a significant difference. The result of this study confirmed the interaction between APOA2 −256T〉C polymorphism and SFAs intake with BMI in type 2 diabetic patients. In fact, homozygous patients for the C allele with high saturated fatty acids intake had higher BMI. The APOA2 −256T〉C polymorphism was associated with elevated levels of serum ghrelin.

Description: The n-3 polyunsaturated fatty acids (PUFAs), EPA and DHA, as well as estrogen have been shown to decrease circulating levels of triglyceride (TG), but their underlying mode of action is unclear. The purpose of this study was to determine the effects of n-3 PUFA consumption and estrogen injection on TG metabolism. Rats ( n  = 48) were fed a modified AIN-93G diet with 0, 1, or 2 % EPA + DHA relative to the total energy intake during 12 weeks. At 8 weeks, rats were ovariectomized (OVX), and after a 1-week recovery, rats were injected with either 17β-estradiol-3-benzoate (E 2 ) or corn oil for the last 3 weeks. The n-3 PUFA consumption and E 2 injection independently decreased the hepatic expressions of sterol regulatory element-binding protein 1, acetyl-CoA carboxylase 1, fatty acid synthase (FAS), and diacylglycerol acyltransferase 2 (DGAT2) ( P  〈 0.05). There were interactions between n-3 PUFA consumption and E 2 injection on hepatic expression of FAS and DGAT2. In addition, n-3 PUFA consumption and E 2 injection up-regulated the expression of AMP-activated protein kinase (AMPK), phosphorylated AMPK, peroxisomal proliferator-activated receptor α, and carnitine palmitoyltransferase 1 in liver and skeletal muscle. E 2 injection increased the expression of estrogen receptor α and β in skeletal muscle and liver, but n-3 PUFA consumption increased the expression of both receptors only in skeletal muscle. The present study suggests that the hypotriglyceridemic effects of n-3 PUFA consumption and E 2 injection could be due to the down-regulation of hepatic TG synthesis and up-regulation of TG oxidation in liver and skeletal muscle in OVX rats.

Description: Black carrots ( Daucus carota L. ) are rich in anthocyanins which contribute many health benefits, but are limited by bioavailability and instability when exposed to oxygen, heat and light. Fermenting black carrots may improve the stability, absorption and bioactivity of its anthocyanins. Here, we examined whether and by what mechanisms the long-term consumption of unfermented black carrot extract (BC) and its extracts fermented with Lactobacillus plantarum (BCLP) or Aspergillus oryzae (BCAO) might prevent menopausal symptoms including impaired energy, glucose and lipid metabolism in estrogen-deficient animals with diet-induced obesity. Ovariectomized (OVX) rats were fed four different high-fat diets containing 2 % dextrin (OVX-control), 2 % BC, 2 % BCLP, or 2 % BCAO for 12 weeks. Sham rats were fed high-fat diets containing 2 % dextrin. The contents of total anthocyanins increased in BCAO compared to BC and BCLP, whereas the contents of cyanidin-3-rutinosides, malvidin-3,5-diglycosides and delphine-3-glucoside were lower and cyanidin and malvidin were much higher in BCLP and BCAO than BC. Fat mass and weight gain were lower in descending order of OVX-control 〉 BC and BCLP 〉 BCAO due to increased energy expenditure and fat oxidation. However, BC, BCLP and especially BCAO all normalized HOMA-IR, an indicator of insulin resistance and glucose intolerance, in OVX rats. OVX increased serum total and LDL cholesterol and triglycerides, but BC, BCLP and BCAO significantly prevented the increases. BCAO markedly decreased hepatic triglyceride levels by increasing gene expressions of CPT-1 and PPAR- α , which are involved in fatty acid oxidation, and decreasing mRNA expressions of FAS and SREBP-1c, which are associated with fatty acid synthesis. This was related to increased pAMPK → pACC signaling and improved hepatic insulin signaling (pAkt → pFOXO-1). Cyanidin and malvidin markedly decreased fat accumulation in 3T3-L1 adipocytes by increasing CPT-1 and decreasing FAS and SREBP-1c expression in comparison with cyanidin-3-rutinoside and malvidin-3,5-diglycosides. In conclusion, with increasing cyanidin and malvidin, BCAO prevented the exacerbation of lipid and glucose metabolism by activating hepatic insulin signaling and AMPK activation by in OVX rats.

Description: Large-scale meta-analyses of genome-wide association studies have recently confirmed that the rs340874 single-nucleotide polymorphism in PROX1 gene is associated with fasting glycemia and type 2 diabetes mellitus; however, the mechanism of this link was not well established. The aim of our study was to evaluate the functional/phenotypic differences related to rs340874 PROX1 variants. The study group comprised 945 subjects of Polish origin (including 634 with BMI 〉 25) without previously known dysglycemia. We analyzed behavioral patterns (diet, physical activity), body fat distribution and glucose/fat metabolism after standardized meals and during the oral glucose tolerance test. We found that the carriers of the rs340874 PROX1 CC genotype had higher nonesterified fatty acids levels after high-fat meal ( p  = 0.035) and lower glucose oxidation ( p  = 0.014) after high-carbohydrate meal in comparison with subjects with other PROX1 genotypes. Moreover, in subjects with CC variant, we found higher accumulation of visceral fat ( p  〈 0.02), but surprisingly lower daily food consumption ( p  〈 0.001). We hypothesize that lipid metabolism alterations in subjects with the PROX1 CC genotype may be a primary cause of higher glucose levels after glucose load, since the fatty acids can inhibit insulin-stimulated glucose uptake by decreasing carbohydrate oxidation. Our observations suggest that the PROX1 variants have pleiotropic effect on disease pathways and it seem to be a very interesting goal of research on prevention of obesity and type 2 diabetes mellitus. The study may help to understand the mechanisms of visceral obesity and type 2 diabetes mellitus risk development.

Description: Chronic inflammation is an important factor in colorectal carcinogenesis. However, evidence on the effect of pro-inflammatory and anti-inflammatory foods and nutrients is scarce. Moreover, there are few studies focusing on diet–gene interactions on inflammation and colorectal cancer (CRC). This study was designed to investigate the association between the novel dietary inflammatory index (DII) and CRC and its potential interaction with polymorphisms in inflammatory genes. Data from the Bellvitge Colorectal Cancer Study, a case–control study (424 cases with incident colorectal cancer and 401 hospital-based controls), were used. The DII score for each participant was obtained by multiplying intakes of dietary components from a validated dietary history questionnaire by literature-based dietary inflammatory weights that reflected the inflammatory potential of components. Data from four important single nucleotide polymorphisms located in genes thought to be important in inflammation-associated CRC: i.e., interleukin ( IL )- 4 , IL-6 , IL-8 , and peroxisome proliferator-activated receptor-γ ( PPARG ) were analyzed. A direct association was observed between DII score and CRC risk (OR Q4 vs. Q1 1.65, 95 % CI 1.05–2.60, and P trend 0.011). A stronger association was found with colon cancer risk (OR Q4 vs. Q1 2.24, 95 % CI 1.33–3.77, and P trend 0.002) than rectal cancer risk (OR Q4 vs. Q1 1.12, 95 % CI 0.61–2.06, and P trend 0.37). DII score was inversely correlated with SNP rs2243250 in IL-4 among controls, and an interaction was observed with CRC risk. Neither correlation nor interaction was detected for other inflammatory genes. Overall, high-DII diets are associated with increased risk of CRC, particularly for colon cancer, suggesting that dietary-mediated inflammation plays an important role in colorectal carcinogenesis.

Description: In e-health intervention studies, there are concerns about the reliability of internet-based, self-reported (SR) data and about the potential for identity fraud. This study introduced and tested a novel procedure for assessing the validity of internet-based, SR identity and validated anthropometric and demographic data via measurements performed face-to-face in a validation study (VS). Participants ( n  = 140) from seven European countries, participating in the Food4Me intervention study which aimed to test the efficacy of personalised nutrition approaches delivered via the internet, were invited to take part in the VS. Participants visited a research centre in each country within 2 weeks of providing SR data via the internet. Participants received detailed instructions on how to perform each measurement. Individual’s identity was checked visually and by repeated collection and analysis of buccal cell DNA for 33 genetic variants. Validation of identity using genomic information showed perfect concordance between SR and VS. Similar results were found for demographic data (age and sex verification). We observed strong intra-class correlation coefficients between SR and VS for anthropometric data (height 0.990, weight 0.994 and BMI 0.983). However, internet-based SR weight was under-reported ( Δ −0.70 kg [−3.6 to 2.1], p  〈 0.0001) and, therefore, BMI was lower for SR data ( Δ −0.29 kg m −2 [−1.5 to 1.0], p  〈 0.0001). BMI classification was correct in 93 % of cases. We demonstrate the utility of genotype information for detection of possible identity fraud in e-health studies and confirm the reliability of internet-based, SR anthropometric and demographic data collected in the Food4Me study. Trial registration : NCT01530139 ( http://clinicaltrials.gov/show/NCT01530139 ).

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: 18β-Glycyrrhetinic acid (18β-GA) has been proposed as a promising hepatoprotective agent. The current study aimed to investigate the protective action and the possible mechanisms of 18β-GA against cyclophosphamide (CP)-induced liver injury in rats, focusing on the role of peroxisome proliferator-activated receptor gamma (PPARγ) and NF-E2-related factor-2 (Nrf2). Rats were administered 18β-GA at doses 25 and 50 mg/kg 2 weeks prior to CP injection. Five days after CP administration, animals were sacrificed and samples were collected. CP induced hepatic damage evidenced by the histopathological changes and significant increase in serum pro-inflammatory cytokines, liver marker enzymes, and liver lipid peroxidation and nitric oxide (NO) levels. 18β-GA counteracted CP-induced oxidative stress and inflammation as assessed by restoration of the antioxidant defenses and diminishing of pro-inflammatory cytokines, lipid peroxidation, and NO production. These hepatoprotective effects appear to depend on activation of Nrf2 and PPARγ, and subsequent suppression of nuclear factor-kappa B. In conclusion, the present study provides evidence that 18β-GA exerts hepatoprotective effects against CP through induction of antioxidant defenses and suppression of inflammatory response. This report also confers new information that 18β-GA protects liver against the toxic effect of chemotherapeutic alkylating agents via activation of Nrf2 and PPARγ.

Description: We investigated the effect of short-term fasting on coordinate changes in the fatty acid composition of adipose triacylglycerol (TAG), serum non-esterified fatty acids (NEFA), liver TAG, and serum TAG and phospholipids in mice fed ad libitum or fasted for 16 h overnight. In contrast to previous reports under conditions of maximal lipolysis, adipose tissue TAG was not preferentially depleted of n-3 PUFA or any specific fatty acids, nor were there any striking changes in the serum NEFA composition. Short-term fasting did, however, increase the hepatic proportion of n-3 PUFA, and almost all individual species of n-3 PUFA showed relative and absolute increases. The relative proportion of n-6 PUFA in liver TAG also increased but to a lesser extent, resulting in a significant decrease in the n-6:n-3 PUFA ratio (from 14.3 ± 2.54 to 9.6 ± 1.20), while the proportion of MUFA decreased significantly and SFA proportion did not change. Examination of genes involved in PUFA synthesis suggested that hepatic changes in the elongation and desaturation of precursor lipids could not explain this effect. Rather, an increase in the expression of fatty acid transporters specific for 22:6n-3 and other long-chain n-3 and n-6 PUFA likely mediated the observed hepatic enrichment. Analysis of serum phospholipids indicated a specific increase in the concentration of 22:6n-3 and 16:0, suggesting increased specific synthesis of DHA-enriched phospholipid by the liver for recirculation. Given the importance of blood phospholipid in distributing DHA to neural tissue, these findings have implications for understanding the adipose–liver–brain axis in n-3 PUFA metabolism.

Description: Survival of motor neuron 2 ( SMN2 ) is a modifier gene for spinal muscular atrophy (SMA), a neurodegenerative disease caused by insufficient SMN protein mostly due to SMN1 defect. SMN2 is nearly identical to SMN1 but unfortunately only able to produce a small amount of SMN protein due to exon 7 skipping. The exon 7-containing SMN2 transcript ( SMN2_ E7+) can be increased by a dietary compound, curcumin, but the involved molecular changes are not clear. Here we have found that in fibroblast cells of a SMA type II patient, curcumin enhanced the inclusion of SMN2 exon 7. Examination of the potential splicing factors showed that curcumin specifically increased the protein and transcript levels of SRSF1. The increased SRSF1 protein was mainly nuclear and hyperphosphorylated. Interestingly, the curcumin effects on the SMN2 and SRSF1 transcripts were inhibited by a protein deacetylase inhibitor, trichostatin A. Moreover, in support of its role in the SMN2 splicing, knocking down SRSF1 reduced the inclusion of SMN2 exon 7. Thus, curcumin appears to have multiple effects on the SMN2 transcript and its splicing regulators, including the change of alternative splicing and transcript/protein level as well as phosphorylation. Protein deacetylases and phosphatases are likely involved in these effects. Interestingly, the effects all seem to favor production of the SMN2 _E7+ transcript in SMA patient cells.

Description: Through a Privacy Calculus (i.e. risk–benefit trade-off) lens, this study identifies factors that contribute to consumers’ adoption of personalised nutrition services. We argue that consumers’ intention to adopt personalised nutrition services is determined by perceptions of Privacy Risk , Personalisation Benefit , Information Control , Information Intrusiveness , Service Effectiveness , and the Benevolence , Integrity , and Ability of a service provider. Data were collected in eight European countries using an online survey. Results confirmed a robust and Europe-wide applicable cognitive model, showing that consumers’ intention to adopt personalised nutrition services depends more on Perceived Personalisation Benefit than on Perceived Privacy Risk . Perceived Privacy Risk was mainly determined by perceptions of Information Control , whereas Perceived Personalisation Benefit primarily depended on Perceived Service Effectiveness . Services that required increasingly intimate personal information, and in particular DNA, raised consumers’ Privacy Risk perceptions, but failed to increase perceptions of Personalisation Benefit . Accordingly, to successfully exploit personalised nutrition, service providers should convey a clear message regarding the benefits and effectiveness of personalised nutrition services. Furthermore, service providers may reduce Privacy Risk by increasing consumer perceptions of Information Control . To enhance perceptions of both Information Control and Service Effectiveness , service providers should make sure that consumers perceive them as competent and reliable.

Description: Human and animal studies suggest an interaction between the Pro12Ala polymorphism of PPARG and dietary fat. In this randomized crossover clinical trial, we investigated whether subjects with the Pro12Pro and Ala12Ala genotypes of PPARG respond differently to a diet supplemented with high saturated (SAFA) or polyunsaturated fatty acid (PUFA).We recruited non-diabetic men from a population-based METSIM study (including 10,197 men) to obtain men with the Ala12Ala and the Pro12Pro genotypes matched for age and body mass index. Seventeen men with the Pro12Pro genotype and 14 with the Ala12Ala genotype were randomized to both a PUFA diet and a SAFA diet for 8 weeks in a crossover setting. Serum lipids and adipose tissue mRNA expression were measured during the diet intervention. At baseline, subjects with the Ala12Ala genotype had higher levels of HDL cholesterol and lower levels of LDL cholesterol, total triglycerides, and apolipoprotein B compared to those subjects with the Pro12Pro genotype ( P  〈 0.05, FDR 〈 0.1). The Ala12Ala genotype also associated with higher mRNA expression of PPARG2, LPIN1, and SREBP - 1c compared to participants with the Pro12Pro genotype (FDR 〈 0.001). On the other hand, PUFA diet resulted in lower levels of fasting glucose, total cholesterol, total triglycerides, and apolipoprotein B ( P  〈 0.05, FDR 〈 0.1) but did not affect PPARG2 mRNA expression in adipose tissue. We conclude that individuals with the Pro12Pro genotype, with higher triglyceride levels at baseline, are more likely to benefit from the PUFA diet. However, the beneficial effects of dietary PUFA and the Ala12Ala genotype of PPARG on serum lipids are mediated through divergent mechanisms.

Description: The usefulness of zinc transporter and metallothionein (MT) gene expressions to detect changes in zinc intake remains unclear. This pilot study aimed to determine the effects of zinc supplementation on zinc transporter and MT gene expressions in humans. Healthy adults ( n  = 39) were randomised to zinc treatment (ZT), receiving 22 mg Zn/day ( n  = 19), or no treatment (NT) ( n  = 20). Blood samples were collected on Days 0, 2, 7, 14, and 21. Plasma zinc and serum C-reactive protein concentrations were analysed. Gene expression of zinc transporters and MT in peripheral blood mononuclear cells was analysed using real-time PCR. Using repeated-measures ANOVA, MT - 2A gene expression and fold change were found to be higher in the ZT group ( P  = 0.025 and P  = 0.016, respectively) compared to the NT group, specifically at Day 2 (40 ± 18 % increase from baseline, P  = 0.011), despite no significant increase in plasma zinc concentration. In a multiple regression model exploring the changes in gene expressions between Days 0 and 21, the change in MT - 2A gene expression was correlated with changes in all zinc transporter expressions ( r 2  = 0.54, P  = 0.029 ); the change in ZIP1 expression emerged as a univariate predictor ( P  = 0.003). Dietary zinc intake was predictive of zinc transporter and MT expressions ( P  = 0.030). Physical activity level was positively correlated with baseline ZIP7 expression ( r  = 0.36, P  = 0.029). The present study shows that MT - 2A expression is related to changing expression of zinc transporter genes, specifically ZIP1 , in response to zinc supplementation. The current report adds to our understanding of MT in the coordinated nature of cellular zinc homeostasis.

Description: Colorectal cancer (CRC) is a disease whose genesis may include metabolic dysregulation. Cancer stem cells are attractive targets for therapeutic interventions since their aberrant expansion may underlie tumor initiation, progression, and recurrence. To investigate the actions of metabolic regulators on cancer stem cell-like cells (CSC) in CRC, we determined the effects of soybean-derived bioactive molecules and the anti-diabetes drug metformin (MET), alone and together, on the growth, survival, and frequency of CSC in human HCT116 cells. Effects of MET (60 μM) and soybean components genistein (Gen, 2 μM), lunasin (Lun, 2 μM), β-conglycinin (β-con, 3 μM), and glycinin (Gly, 3 μM) on HCT116 cell proliferation, apoptosis, and mRNA/protein expression and on the frequency of the CSC CD133 + CD44 + subpopulation by colonosphere assay and fluorescence-activated cell sorting/flow cytometry were evaluated. MET, Gen, and Lun, individually and together, inhibited HCT116 viability and colonosphere formation and, conversely, enhanced HCT116 apoptosis. Reductions in frequency of the CSC CD133 + CD44 + subpopulation with MET, Gen, and Lun were found to be associated with increased PTEN and reduced FASN expression. In cells under a hyperinsulinemic state mimicking metabolic dysregulation and without and with added PTEN-specific inhibitor SF1670, colonosphere formation and frequency of the CD133 + CD44 + subpopulation were decreased by MET, Lun and Gen, alone and when combined. Moreover, MET + Lun + Gen co-treatment increased the pro-apoptotic and CD133 + CD44 + -inhibitory efficacy of 5-fluorouracil under hyperinsulinemic conditions. Results identify molecular networks shared by MET and bioavailable soy food components, which potentially may be harnessed to increase drug efficacy in diabetic and non-diabetic patients with CRC.

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