ALBERT

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〉 〈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〉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〉Evidence suggests that prenatal exposure to 〈em〉n-3〈/em〉 long-chain polyunsaturated fatty acids (LCPUFA) reduces the incidence of allergic disease in children. LCPUFAs are produced from dietary precursors catalyzed by desaturases and elongases encoded by the 〈em〉FADS1/2〈/em〉 and 〈em〉ELOVL5〈/em〉 genes. DNA methylation regulates gene activity and fatty acid supplementation could alter DNA methylation (DNA-M) at these genes. We investigated whether DNA-M and expression of the 〈em〉FADS1/2〈/em〉 and 〈em〉ELOVL5〈/em〉 genes were associated with allergy in children and gestational fish intake. We studied 170 participants from the Isle of Wight 3rd Generation Cohort, UK. Phenotype data and exposure was assessed by questionnaires. Genome-wide DNA-M in cord blood samples was quantified using the Illumina Infinium HumanMethylation450 and EPIC Beadchips. Five SNPs (single-nucleotide polymorphisms) in the 〈em〉FADS〈/em〉 gene cluster and one SNP in 〈em〉ELOVL5〈/em〉 were genotyped in offspring. 〈em〉FADS〈/em〉 gene expression in offspring cord blood was determined.〈/p〉 〈/span〉 〈span〉 〈h3〉Results〈/h3〉 〈p〉Gestational fish intake was significantly associated with increased methylation of cg12517394 (〈em〉P〈/em〉 = 0.049), which positively correlated with 〈em〉FADS1〈/em〉 mRNA levels (〈em〉P〈/em〉 = 0.021). 〈em〉ELOVL5〈/em〉 rs2397142 was significantly associated with eczema (〈em〉P〈/em〉 = 0.011) and methylation at cg11748354 and cg24524396 (〈em〉P〈/em〉 〈 0.001 and 〈em〉P〈/em〉 = 0.036, respectively). Gestational fish intake was strongly associated with elevated DNA-M at cg11748354 and cg24524396 (〈em〉P〈/em〉 = 0.029 and 〈em〉P〈/em〉 = 0.002, respectively) and reduced 〈em〉ELOVL5〈/em〉 mRNA expression (〈em〉P〈/em〉 = 0.028).〈/p〉 〈/span〉 〈span〉 〈h3〉Conclusion〈/h3〉 〈p〉The association between induced 〈em〉FADS1/2〈/em〉 and 〈em〉ELOVL5〈/em〉 DNA-M and reduced gene expression due to gestational fish intake provide a mechanistic explanation of the previously observed association between maternal LCPUFA intake and allergy development in early childhood.〈/p〉 〈/span〉

Description: 〈h3〉Abstract〈/h3〉 〈span〉 〈h3〉Background/objectives〈/h3〉 〈p〉Cereal foods are major contributors to the daily energy, protein, and dietary fiber intake all over the world. The role of cereals in human health is dependent on whether they are consumed as refined or whole grain and on cereal species. To unravel the underlying mechanisms of health effects attributed to specific cereal foods and to provide more precise dietary advice, there is a need for improved dietary assessment of whole-grain intake. Dietary biomarkers of specific cereals, different fractions or cereal-containing foods could offer such a possibility. The aim of this review was to summarize the current status on biomarkers of different cereals, fractions, and specific cereal foods.〈/p〉 〈/span〉 〈span〉 〈h3〉Subjects and methods〈/h3〉 〈p〉A literature review was conducted and putative biomarkers of different cereals and pseudo-cereals (wheat, oats, rye, barley, rice, and quinoa) as well as for different grain fractions (whole grain, refined grain, bran) and foods were summarized and discussed.〈/p〉 〈/span〉 〈span〉 〈h3〉Results〈/h3〉 〈p〉Several putative biomarkers have been suggested for different cereals, due to their unique presence in these grains. Among the biomarkers, odd-numbered alkylresorcinols are the most well-studied and -evaluated biomarkers and reflect whole-grain wheat and rye intake. Even-numbered alkylresorcinols have been suggested to reflect quinoa intake. Recent studies have also highlighted the potential of avenanthramides and avenacosides as specific biomarkers of oat intake, and a set of biomarkers have been suggested to reflect rice bran intake. However, there are yet no specific biomarkers of refined grains. Most biomarker candidates remain to be evaluated in controlled interventions and free-living populations before applied as biomarkers of intake in food and health studies.〈/p〉 〈/span〉 〈span〉 〈h3〉Conclusion〈/h3〉 〈p〉Several putative biomarkers of different cereals have been suggested and should be validated in human studies using recently developed food intake biomarker validation criteria.〈/p〉 〈/span〉

Description: 〈h3〉Abstract〈/h3〉 〈span〉 〈h3〉Background〈/h3〉 〈p〉Metabolic flexibility is the ability of an organism to switch between substrates for energy metabolism, in response to the changing nutritional state and needs of the organism. On the cellular level, metabolic flexibility revolves around the tricarboxylic acid cycle by switching acetyl coenzyme A production from glucose to fatty acids and vice versa. In this study, we modelled cellular metabolic flexibility by constructing a logical model connecting glycolysis, fatty acid oxidation, fatty acid synthesis and the tricarboxylic acid cycle, and then using network analysis to study the behaviours of the model.〈/p〉 〈/span〉 〈span〉 〈h3〉Results〈/h3〉 〈p〉We observed that the substrate switching usually occurs through the inhibition of pyruvate dehydrogenase complex (PDC) by pyruvate dehydrogenase kinases (PDK), which moves the metabolism from glycolysis to fatty acid oxidation. Furthermore, we were able to verify four different regulatory models of PDK to contain known biological observations, leading to the biological plausibility of all four models across different cells and conditions.〈/p〉 〈/span〉 〈span〉 〈h3〉Conclusion〈/h3〉 〈p〉These results suggest that the cellular metabolic flexibility depends upon the PDC-PDK regulatory interaction as a key regulatory switch for changing metabolic substrates.〈/p〉 〈/span〉

Description: 〈h3〉Abstract〈/h3〉 〈span〉 〈h3〉Background〈/h3〉 〈p〉Low vitamin B12 concentrations have been associated with major clinical outcomes, including adiposity, in Indian populations. The Fat mass and obesity-associated gene (〈em〉FTO〈/em〉) is an established obesity-susceptibility locus; however, it remains unknown whether it influences vitamin B12 status. Hence, we investigated the association of two previously studied 〈em〉FTO〈/em〉 polymorphisms with vitamin B12 concentrations and metabolic disease-related outcomes and examined whether these associations were modified by dietary factors and physical activity.〈/p〉 〈/span〉 〈span〉 〈h3〉Methods〈/h3〉 〈p〉A total of 176 individuals with type 2 diabetes, 152 with pre-diabetes, and 220 normal glucose-tolerant individuals were randomly selected from the Chennai Urban Rural Epidemiology Study. Anthropometric, clinical, and biochemical investigations, which included body mass index (BMI), waist circumference, vitamin B12, homocysteine, and folic acid were measured. A validated food frequency questionnaire was used for dietary assessment and self-reported physical activity measures were collected. An unweighted genetic risk score (GRS) was calculated for two 〈em〉FTO〈/em〉 single-nucleotide polymorphisms (rs8050136 and rs2388405) by summation of the number of risk alleles for obesity. Interaction analyses were performed by including the interaction terms in the regression model.〈/p〉 〈/span〉 〈span〉 〈h3〉Results〈/h3〉 〈p〉The GRS was significantly associated with increased BMI (〈em〉P〈/em〉 = 0.009) and risk of obesity (〈em〉P〈/em〉 = 0.023). Individuals carrying more than one risk allele for the GRS had 13.13% lower vitamin B12 concentrations, compared to individuals carrying zero risk alleles (〈em〉P〈/em〉 = 0.018). No associations between the GRS and folic acid and homocysteine concentrations were observed. Furthermore, no statistically significant GRS-diet or GRS-physical activity interactions with vitamin B12, folic acid, homocysteine or metabolic-disease outcomes were observed.〈/p〉 〈/span〉 〈span〉 〈h3〉Conclusion〈/h3〉 〈p〉The study shows for the first time that a genetic risk score using two 〈em〉FTO〈/em〉 SNPs is associated with lower vitamin B12 concentrations; however, we did not identify any evidence for the influence of lifestyle factors on this association. Further replication studies in larger cohorts are warranted to investigate the association between the GRS and vitamin B12 concentrations.〈/p〉 〈/span〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉Tubers are important crops as well as staple foods in human nutrition. Among tubers, the potato in particular has been investigated for its health effects. However, except for its contribution to energy and effects related to resistant starch, the role of potatoes and other tubers in human health is still debated. In order to establish firm evidence for the health effects of dietary tubers and processed tuber products, it is essential to assess total intake accurately. The dietary assessment in most studies relies mainly on self-reporting and may give imprecise quantitative information on dietary intakes. Biomarkers of food intake (BFIs) are useful objective means to assess intake of specific foods or may be used as an additional measure to calibrate the measurement error in dietary reports. Here, intake biomarkers for common tubers, including potatoes and heated potato products, sweet potato, cassava, yam, and Jerusalem artichoke, are reviewed according to the biomarker of food intake reviews (BFIRev) standardized protocols for review and validation. Candidate BFIs for heated potato product include α-chaconine, α-solanine, and solanidine; less evidence is available to indicate peonidin 3-caffeoylsophoroside-5-glucoside and cyanidin 3-caffeoylsophoroside-5-glucoside as putative biomarkers having high potential specificity for purple sweet potato intake; linamarin may in addition be considered as a putative BFI for cassava. Other tubers also contain toxic glycosides or common contaminants as characteristic components but their putative use as intake biomarkers is not well documented. Alkyl pyrazines, acrylamide, and acrolein are formed during cooking of heated potato products while these have not yet been investigated for other tubers; these markers may not be specific only to heated potato but measurements of these compounds in blood or urine may be combined with more specific markers of the heated products, e.g., with glycoalkaloids to assess heated potato products consumption. Further studies are needed to assess the specificity, robustness, reliability, and analytical performance for the candidate tuber intake biomarkers identified in this review.〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉The fruit fly 〈em〉Drosophila melanogaster〈/em〉 has been increasingly recognized as an important model organism in nutrition research. In order to conduct nutritional studies in fruit flies, special attention should be given to the composition of the experimental diets. Besides complex diets, which are often based on maize, yeast, sucrose, and agar, 〈em〉Drosophila〈/em〉 can be also fed chemically defined diets. These so-called holidic diets are standardized in terms of their macro- and micronutrient composition although the quantitative nutrient requirements of flies have yet not been fully established and warrant further investigations. For instance, only few studies address the fatty acid, vitamin, mineral, and trace element requirements of fruit flies. 〈em〉D. melanogaster〈/em〉 may be also of interest in the field of nutritional medicine. Diet-induced diabetes and obesity models have been established, and in this context, often, the so-called high-fat and high-sugar diets are fed. However, the composition of these diets is not sufficiently defined and varies between studies. A consensus within the scientific community needs to be reached to standardize the exact composition of experimental complex and holidic diets for 〈em〉D. melanogaster〈/em〉 in nutrition research. Since 〈em〉D. melanogaster〈/em〉 is an established valuable model system for numerous human diseases, standardized diets are also a prerequisite to conduct diet-disease interaction studies. We suggest that a comprehensive approach, which combines deep phenotyping with disease-related 〈em〉Drosophila〈/em〉 models under defined dietary conditions, might lead to the foundation of a so-called fly clinic.〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈span〉 〈h3〉Objective〈/h3〉 〈p〉The purpose of this study was to draw a global portrait of the current knowledge and interest regarding nutrigenetics in a population of French Canadians from the province of Quebec (Canada).〈/p〉 〈/span〉 〈span〉 〈h3〉Methods〈/h3〉 〈p〉A total of 2238 residents from the province of Quebec, Canada, were recruited via social networks and from the Laval University employee/student lists to participate in a 37-question online survey on nutrigenetics.〈/p〉 〈/span〉 〈span〉 〈h3〉Results〈/h3〉 〈p〉Most participants were not familiar with the term “nutrigenetics” (82.7%). Participants with good genetic literacy (26.8%) were less interested in nutrigenetic testing (〈em〉p〈/em〉 〈 0.0001). The vast majority of participants (90.7%) reported to be willing to follow a personalised diet based on nutrigenetic testing, especially if they came to know themselves as carriers of a polymorphism increasing the risk of certain diseases. Participants had a higher interest in testing related to metabolic response to macronutrients (types of sugars, fats and proteins) than to micronutrients or other nutrients related to food intolerance.〈/p〉 〈/span〉 〈span〉 〈h3〉Conclusions〈/h3〉 〈p〉The attitude of French Canadians about nutrigenetics is very consistent with the results from other surveys published in the literature. Although few individuals are familiar with nutrigenetics, the public’s attitude towards nutrigenetics is globally favourable.〈/p〉 〈/span〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉Nuts and vegetable oils are important sources of fat and of a wide variety of micronutrients and phytochemicals. Following their intake, several of their constituents, as well as their derived metabolites, are found in blood circulation and in urine. As a consequence, these could be used to assess the compliance to a dietary intervention or to determine habitual intake of nuts and vegetable oils. However, before these metabolites can be widely used as biomarkers of food intake (BFIs), several characteristics have to be considered, including specificity, dose response, time response, stability, and analytical performance. We have, therefore, conducted an extensive literature search to evaluate current knowledge about potential BFIs of nuts and vegetable oils. Once identified, the strengths and weaknesses of the most promising candidate BFIs have been summarized. Results from selected studies have provided a variety of compounds mainly derived from the fatty fraction of these foods, but also other components and derived metabolites related to their nutritional composition. In particular, α-linolenic acid, urolithins, and 5-hydroxyindole-3-acetic acid seem to be the most plausible candidate BFIs for walnuts, whereas for almonds they could be α-tocopherol and some catechin-derived metabolites. Similarly, several studies have reported a strong association between selenium levels and consumption of Brazil nuts. Intake of vegetable oils has been mainly assessed through the measurement of specific fatty acids in different blood fractions, such as oleic acid for olive oil, α-linolenic acid for flaxseed (linseed) and rapeseed (canola) oils, and linoleic acid for sunflower oil. Additionally, hydroxytyrosol and its metabolites were the most promising distinctive BFIs for (extra) virgin olive oil. However, most of these components lack sufficient specificity to serve as BFIs. Therefore, additional studies are necessary to discover new candidate BFIs, as well as to further evaluate the specificity, sensitivity, dose-response relationships, and reproducibility of these candidate biomarkers and to eventually validate them in other populations. For the discovery of new candidate BFIs, an untargeted metabolomics approach may be the most effective strategy, whereas for increasing the specificity of the evaluation of food consumption, this could be a combination of different metabolites.〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈span〉 〈h3〉Background〈/h3〉 〈p〉The present study was conducted to investigate the effects of gastric infusion of short-chain fatty acids (SCFA) on gut barrier function in a pig model. In this study, 21 DLY barrows with an average initial body weight of (8.31 ± 0.72) kg were randomly allotted into three treatments: (1) control, (2) infusing low SCFA, S1, (3) infusing high SCFA, S2. The experimental period lasted for 7 days.〈/p〉 〈/span〉 〈span〉 〈h3〉Results〈/h3〉 〈p〉Gastric infusion of SCFA increased the concentrations of SCFA in serum and digesta, and enhanced the mRNA and protein abundances of SCFA receptors in pig intestine (〈em〉P〈/em〉 〈 0.05). Moreover, gastric infusion of SCFA led to alteration of intestinal morphology, elevation of intestinal development-related gene abundances, and decrease of apoptotic cell percentage, as well as reduction of pro-apoptosis gene and protein abundances (〈em〉P〈/em〉 〈 0.05). Besides, the jejunal SLC〈sub〉7〈/sub〉A〈sub〉1〈/sub〉 and ileal DMT1 mRNA abundances in the SCFA infusion groups were higher than those in the control group (〈em〉P〈/em〉 〈 0.05). Additionally, gastric infusion of SCFA increased the mRNA abundances of Occludin and Claudin-1 in the duodenum and ileum, enhanced 〈em〉Lactobacillus〈/em〉 spp counts in the ileal digesta, decreased the mRNA and protein abundances of IL-1β in the colon, and reduced 〈em〉Escherichia coli〈/em〉 count in the ileal digesta (〈em〉P〈/em〉 〈 0.05).〈/p〉 〈/span〉 〈span〉 〈h3〉Conclusions〈/h3〉 〈p〉These data indicated that gastric infusion of SCFA, especially high SCFA concentration, may be beneficial to gut development of piglets via improving gut morphology, decreasing apoptotic cell percentage, and maintaining intestinal barrier function.〈/p〉 〈/span〉

Description: 〈h3〉Abstract〈/h3〉 〈span〉 〈h3〉Background〈/h3〉 〈p〉Micro algae’s are worldwide considered as an alternative source of proteins in diets for animals and humans. Micro algae also produce an array of biological active substances with potential to induce beneficial and health promoting effects. To better understand the mode of action of micro algae’s when applied as additive in diets, porcine intestinal epithelial cells (IPEC-J2), stressed by enterotoxigenic 〈em〉Escherichia coli〈/em〉 (ETEC) or under non-stressed conditions, were exposed to micro algae extracts and changes in gene expression were recorded.〈/p〉 〈/span〉 〈span〉 〈h3〉Methods〈/h3〉 〈p〉IPEC-J2 cells were exposed for 2 and 6 h to extracts prepared from the biomass of the microalgae 〈em〉Chlorella vulgaris〈/em〉 (C), 〈em〉Haematococcus pluvialis〈/em〉 (H), 〈em〉Spirulina platensis〈/em〉 (S), or a mixture of S〈em〉cenedesmus obliques〈/em〉 and 〈em〉Chlorella sorokiniana〈/em〉 (AM), in the absence and presence of ETEC. Gene expression in cells was measured using porcine “whole genome” microarrays.〈/p〉 〈/span〉 〈span〉 〈h3〉Results〈/h3〉 〈p〉The micro algae extracts alone enhanced the expression of a set of genes coding for proteins with biological activity that are secreted from cells. These secreted proteins (hereafter denoted as effector proteins; EPs) may regulate processes like remodelling of the extracellular matrix, activation of an antiviral/bacterial response and oxygen homeostasis in the intestine and periphery. Elevated gene expression of immunostimulatory proteins CCL17, CXCL2, CXCL8 (alias IL8), IFNA, IFNL1, HMOX1, ITGB3, and THBS1 was observed in response to all four extracts in the absence or presence of ETEC. For several of these immunostimulatory proteins no elevated expression was observed when cells were exposed to ETEC alone. Furthermore, all extracts highly stimulated expression of an antisense RNA of the mitochondrial/peroxisome symporter SLC25A21 gene in ETEC-challenged cells. Inhibition of SLC25A21 translation by this antisense RNA may impose a concentration gradient of 2-oxoadipic and 2-oxoglutarate, both metabolites of fatty acid β-oxidation, between the cytoplasm and the interior of these organelles.〈/p〉 〈/span〉 〈span〉 〈h3〉Conclusions〈/h3〉 〈p〉Exposure of by ETEC stressed intestinal epithelium cells to micro algae extracts affected “fatty acid β-oxidation”, ATP and reactive oxygen species production and (de) hydroxylation of lysine residues in procollagen chains in these cells. Elevated gene expression of specific EPs and immunostimulatory proteins indicated that micro algae extracts, when used as feed/food additive, can steer an array of metabolic and immunological processes in the intestines of humans and monogastric animals stressed by an enteric bacterial pathogen.〈/p〉 〈/span〉

Description: 〈h3〉Abstract〈/h3〉 〈span〉 〈h3〉Background〈/h3〉 〈p〉Studies have shown that the effects of maternal nutrition exposure during gestation influence metabolic risk in early life through an epigenetic mechanism. Low glycaemic index (GI) diets benefit both maternal and neonatal gestational outcomes. We hypothesize that maternal dietary GI or glycaemic load (GL) changes during pregnancy impact placental DNA methylation, especially in insulin resistance-related genes.〈/p〉 〈/span〉 〈span〉 〈h3〉Methods〈/h3〉 〈p〉From a clinical trial of overweight pregnant women, 12 subjects who successfully reduced their GI and another 12 whose GI increased despite the intervention were selected. A genome-wide differential methylation analysis of placental tissue DNA was conducted, followed by bioinformatic annotation and validation analysis. The distribution of genome-wide differentially methylated regions (DMRs) and CpG sites was described. Six CpG sites in regulatory regions of four insulin-related genes (〈em〉PLIN1〈/em〉, 〈em〉CPT1B〈/em〉, 〈em〉SSTR4〈/em〉, and 〈em〉CIDEA〈/em〉) were selectively validated by pyrosequencing. Pairwise Spearman correlation analysis was performed to test methylation–phenotype association in an additional 153 subjects from the same trial. Correlation between methylation of significant sites and placental mRNA expression of 〈em〉SSTR4〈/em〉 was also analysed.〈/p〉 〈/span〉 〈span〉 〈h3〉Results〈/h3〉 〈p〉Dietary GI decreased by 24.3 (26.2–20.1) in the group who responded appropriately to the intervention and increased by 19.6 (15.2–29.1) in the comparison group. Epigenome-wide analysis identified 108 DMRs and 365 CpG sites with 〈em〉P〈/em〉 〈 0.05 adjusted by false discovery rate, distributed over all chromosomes. The methylation level of cg05009389 in the 3′ UTR of 〈em〉PLIN1〈/em〉 was negatively correlated with maternal weight gain (〈em〉ρ〈/em〉 = − 0.21, 〈em〉P〈/em〉 = 0.027) and increase in insulin levels (〈em〉ρ〈/em〉 = − 0.24, 〈em〉P〈/em〉 = 0.015) during gestation. Methylation levels of cg17586860 and cg18197392 in the 5′ UTR region of 〈em〉SSTR4〈/em〉 were negatively correlated with changes in dietary carbohydrate intake (〈em〉ρ〈/em〉 = − 0.24, 〈em〉P〈/em〉s ≤ 0.006) and GL across gestation (〈em〉ρ〈/em〉 = − 0.23, 〈em〉P〈/em〉s ≤ .008). This correlation survived the adjustment for maternal factors such as dietary GI, body mass index, and gestational diabetes. Up to 89% of cg18197392 methylation was explained by GL change. Cg14631053 methylation correlated positively with mRNA expression of 〈em〉SSTR4〈/em〉 in the placenta (〈em〉ρ〈/em〉 = 0.20, 〈em〉P〈/em〉 = 0.037)〈em〉.〈/em〉〈/p〉 〈/span〉 〈span〉 〈h3〉Conclusions〈/h3〉 〈p〉We provide the first evidence that maternal dietary GI changes during gestation may impact placental DNA methylation of insulin regulation genes. This supports the hypothesis that placental methylation may be the epigenetic mechanism through which maternal diet influences the metabolic health of offspring.〈/p〉 〈/span〉

Description: 〈h3〉Abstract〈/h3〉 〈span〉 〈h3〉Background〈/h3〉 〈p〉Variability in circulating carotenoids may be attributable to several factors including, among others, genetic variants and lipid profile. However, relatively few studies have considered the impact of gene expression in the inter-individual variability in circulating carotenoids. Most studies considered expression of genes individually and ignored their high degree of interconnection. Weighted gene co-expression network analysis (WGCNA) is a systems biology method used for finding gene clusters with highly correlated expression levels and for relating them to phenotypic traits. The objective of the present observational study is to examine the relationship between plasma total carotenoid concentrations and lipid profile using WGCNA.〈/p〉 〈/span〉 〈span〉 〈h3〉Results〈/h3〉 〈p〉Whole blood expression levels of 533 probes were associated with plasma total carotenoids. Among the four WGCNA distinct modules identified, turquoise, blue, and brown modules correlated with plasma high-density lipoprotein cholesterol (HDL-C) and total cholesterol. Probes showing a strong association with HDL-C and total cholesterol were also the most important elements of the brown and blue modules. A total of four and 29 hub genes associated with total carotenoids were potentially related to HDL-C and total cholesterol, respectively.〈/p〉 〈/span〉 〈span〉 〈h3〉Conclusions〈/h3〉 〈p〉Expression levels of 533 probes were associated with plasma total carotenoid concentrations. Using WGCNA, four modules and several hub genes related to lipid and carotenoid metabolism were identified. This integrative analysis provides evidence for the potential role of gene co-expression in the relationship between carotenoids and lipid concentrations. Further studies and validation of the hub genes are needed.〈/p〉 〈/span〉

Description: 〈h3〉Abstract〈/h3〉 〈span〉 〈h3〉Background〈/h3〉 〈p〉Genetically mediated sensitivity to bitter taste has been associated with food preferences and eating behavior in adults and children. The aim of this study was to assess the association between TAS2R38 bitter taste genotype and the first complementary food acceptance in infants.〈/p〉 〈p〉Parents of healthy, breastfed, term-born infants were instructed, at discharge from the nursery, to feed their baby with a first complementary meal of 150 mL at 4 to 6 months of age. They recorded the day when the child ate the whole meal in a questionnaire. Additional data included food composition, breastfeeding duration, feeding practices, and growth at 6 months. Infants’ TAS2R38 genotypes were determined at birth, and infants were classified as “bitter-insensitive” (genotype AVI/AVI) and “bitter-sensitive” (genotypes AVI/PAV or PAV/PAV).〈/p〉 〈/span〉 〈span〉 〈h3〉Results〈/h3〉 〈p〉One hundred seventy-six infants and their mothers were enrolled; completed data were available for 131/176 (74.4%) infants (gestational age 39.3 ± 1.1 weeks, birth weight 3390 ± 430 g). Bitter-insensitive were 45/131 (34.3%), and bitter-sensitive were 86/131 (65.6%). Thirty-one percent of bitter-insensitive infants consumed the whole complementary meal at first attempt, versus 13% of bitter-sensitive ones (〈em〉p〈/em〉 = 0.006). This difference was significant independently of confounding variables such as sex, breastfeeding, or foods used in the meal. Growth at 6 months did not differ between the two groups.〈/p〉 〈/span〉 〈span〉 〈h3〉Conclusions〈/h3〉 〈p〉Differences in 〈em〉TAS2R38〈/em〉 bitter taste gene were associated with acceptance of the first complementary food in infants, suggesting a possible involvement in eating behavior at weaning.〈/p〉 〈/span〉

Description: 〈h3〉Abstract〈/h3〉 〈span〉 〈h3〉Background〈/h3〉 〈p〉A low-protein diet increases the expression and circulating concentration of FGF21. FGF21 stimulates the browning process of WAT by enhancing the expression of UCP1 coupled with an increase in PGC1α. Interestingly, the consumption of a low-protein diet could stimulate WAT differentiation into beige/brite cells by increasing FGF21 expression and 〈em〉Ucp1〈/em〉 mRNA abundance. However, whether the stimulus of a low-protein diet on WAT browning can synergistically interact with another browning stimulus, such as cold exposure, remains elusive.〈/p〉 〈/span〉 〈span〉 〈h3〉Results〈/h3〉 〈p〉In the present study, rats were fed 6% (low), 20% (adequate), or 50% (high) dietary protein for 10 days and subsequently exposed to 4 °C for 72 h. Body weight, food intake, and energy expenditure were measured, as well as WAT browning and BAT thermogenesis markers and FGF21 circulating levels. The results showed that during cold exposure, the consumption of a high-protein diet reduced UCP1, TBX1, 〈em〉Cidea〈/em〉, 〈em〉Cd137〈/em〉, and 〈em〉Prdm16〈/em〉 in WAT when compared with the consumption of a low-protein diet. In contrast, at room temperature, a low-protein diet increased the expression of UCP1, 〈em〉Cidea〈/em〉, and 〈em〉Prdm16〈/em〉 associated with an increase in FGF21 expression and circulating levels when compared with a consumption of a high-protein diet. Consequently, the consumption of a low-protein diet increased energy expenditure.〈/p〉 〈/span〉 〈span〉 〈h3〉Conclusions〈/h3〉 〈p〉These results indicate that in addition to the environmental temperature, WAT browning is nutritionally modulated by dietary protein, affecting whole-body energy expenditure.〈/p〉 〈/span〉 〈span〉 〈h3〉Graphical abstract〈/h3〉 〈p〉 〈span〉 〈span〉 〈img alt="" src="https://static-content.springer.com/image/MediaObjects/12263_2019_642_Figa_HTML.png"〉 〈/span〉 〈/span〉 〈/p〉 〈/span〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉Culinary herbs and spices have been used as both food flavoring and food preservative agents for centuries. Moreover, due to their known and presumptive health benefits, herbs and spices have also been used in medical practices since ancient times. Some of the health effects attributed to herbs and spices include antioxidant, anti-microbial, and anti-inflammatory effects as well as potential protection against cardiovascular disease, neurodegeneration, type 2 diabetes, and cancer. While interest in herbs and spices as medicinal agents remains high and their use in foods continues to grow, there have been remarkably few studies that have attempted to track the dietary intake of herbs and spices and even fewer that have tried to find potential biomarkers of food intake (BFIs). The aim of the present review is to systematically survey the global literature on herbs and spices in an effort to identify and evaluate specific intake biomarkers for a representative set of common herbs and spices in humans. A total of 25 herbs and spices were initially chosen, including anise, basil, black pepper, caraway, chili pepper, cinnamon, clove, cumin, curcumin, dill, fennel, fenugreek, ginger, lemongrass, marjoram, nutmeg, oregano, parsley, peppermint and spearmint, rosemary, saffron, sage, tarragon, and thyme. However, only 17 of these herbs and spices had published, peer-reviewed studies describing potential biomarkers of intake. In many studies, the herb or spice of interest was administrated in the form of a capsule or extract and very few studies were performed with actual foods. A systematic assessment of the candidate biomarkers was also performed. Given the limitations in the experimental designs for many of the published studies, further work is needed to better evaluate the identified set of BFIs. Although the daily intake of herbs and spices is very low compared to most other foods, this important set of food seasoning agents should not be underestimated, especially given their potential benefits to human health.〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈span〉 〈h3〉Background〈/h3〉 〈p〉Hepatic insulin resistance (IR) plays a crucial role in the development of many metabolic diseases, such as type 2 diabetes. MicroRNAs (miRNAs) are involved in the pathogenesis of IR and related diseases; however, studies of miRNAs in hepatic IR are limited.〈/p〉 〈/span〉 〈span〉 〈h3〉Method〈/h3〉 〈p〉In this study, we adopted a high-throughput sequencing approach to construct small RNA libraries in the livers of normal mice and high-fat diet-induced hepatic IR mice.〈/p〉 〈/span〉 〈span〉 〈h3〉Results〈/h3〉 〈p〉Through analysis of data, 107 known and 56 novel miRNAs were identified as differentially expressed miRNAs between the two groups. Additionally, bioinformatics methods were used to predict targets of the differentially expressed miRNAs and to explore the potential downstream Gene Ontology categories and Kyoto Encyclopedia of Genes and Genomes pathways. Meanwhile, some differentially expressed miRNAs (〈em〉miR-34a-5p〈/em〉, 〈em〉miR-149-5p〈/em〉, 〈em〉miR-335-3p〈/em〉, 〈em〉miR-10b-5p〈/em〉, 〈em〉miR-1a-3p〈/em〉, 〈em〉miR-411-5p〈/em〉, and 〈em〉miR-592-5p〈/em〉) were validated by quantitative-time PCR, and their potential target genes related to IR or glycolipid metabolism were also predicted and presented in this study.〈/p〉 〈/span〉 〈span〉 〈h3〉Conclusion〈/h3〉 〈p〉Taken together, our results defined miRNA expression signature that may lead to hepatic IR in mice, and the findings provided a foundation for future studies to further explore the effects and underlying mechanisms of the miRNAs and their target genes in the pathogenesis of hepatic IR and related diseases.〈/p〉 〈/span〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉Animals require sufficient intake of a variety of nutrients to support their development, somatic maintenance and reproduction. An adequate diet provides cell building blocks, chemical energy to drive cellular processes and essential nutrients that cannot be synthesised by the animal, or at least not in the required amounts. Dietary requirements of nematodes, including 〈em〉Caenorhabditis elegans〈/em〉 have been extensively studied with the major aim to develop a chemically defined axenic medium that would support their growth and reproduction. At the same time, these studies helped elucidating important aspects of nutrition-related biochemistry and metabolism as well as the establishment of 〈em〉C. elegans〈/em〉 as a powerful model in studying evolutionarily conserved pathways, and the influence of the diet on health.〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉Nutrigenomics explains the interaction between the genome, the proteome, the epigenome, the metabolome, and the microbiome with the nutritional environment of an organism. It is therefore situated at the interface between an organism’s health, its diet, and the genome.〈/p〉 〈p〉The diet and/or specific dietary compounds are able to affect not only the gene expression patterns, but also the epigenetic mechanisms as well as the production of metabolites and the bacterial composition of the microbiota. 〈em〉Drosophila melanogaster〈/em〉 provides a well-suited model organism to unravel these interactions in the context of nutrigenomics as it combines several advantages including an affordable maintenance, a short generation time, a high fecundity, a relatively short life expectancy, a well-characterized genome, and the availability of several mutant fly lines. Furthermore, it hosts a mammalian-like intestinal system with a clear microbiota and a fat body resembling the adipose tissue with liver-equivalent oenocytes, supporting the fly as an excellent model organism not only in nutrigenomics but also in nutritional research. Experimental approaches that are essentially needed in nutrigenomic research, including several sequencing technologies, have already been established in the fruit fly. However, studies investigating the interaction of a specific diet and/or dietary compounds in the fly are currently very limited.〈/p〉 〈p〉The present review provides an overview of the fly’s morphology including the intestinal microbiome and antimicrobial peptides as modulators of the immune system. Additionally, it summarizes nutrigenomic approaches in the fruit fly helping to elucidate host-genome interactions with the nutritional environment in the model organism 〈em〉Drosophila melanogaster〈/em〉.〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉Aging is a complex phenomenon caused by the time-dependent loss of cellular homeodynamics and consequently of physiological organismal functions. This process is affected by both genetic and environmental (e.g., diet) factors, as well as by their constant interaction. Consistently, deregulation of nutrient sensing and signaling pathways is considered a hallmark of aging. Nutrigenomics is an emerging scientific discipline that studies changes induced by diet on the genome and thus it considers the intersection of three topics, namely health, diet, and genomics. Model organisms, such as the fruit fly 〈em〉Drosophila melanogaster〈/em〉, have been successfully used for in vivo modeling of higher metazoans aging and for nutrigenomic studies. 〈em〉Drosophila〈/em〉 is a well-studied organism with sophisticated genetics and a fully annotated sequenced genome, in which ~ 75% of human disease-related genes have functional orthologs. Also, flies have organs/tissues that perform the equivalent functions of most mammalian organs, while discrete clusters of cells maintain insect carbohydrate homeostasis in a way similar to pancreatic cells. Herein, we discuss the mechanistic connections between nutrition and aging in 〈em〉Drosophila〈/em〉, and how this model organism can be used to study the effect of different diets (including natural products and/or their derivatives) on higher metazoans longevity.〈/p〉

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〉 〈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〉 〈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: Humans are not autonomous entities. We are all living in a complex environment, interacting not only with our peers, but as true holobionts; we are also very much in interaction with our coexisting microbial ecosystems living on and especially within us, in the intestine. Intestinal microorganisms, often collectively referred to as intestinal microbiota, contribute significantly to our daily energy uptake by breaking down complex carbohydrates into simple sugars, which are fermented to short-chain fatty acids and subsequently absorbed by human cells. They also have an impact on our immune system, by suppressing or enhancing the growth of malevolent and beneficial microbes. Our lifestyle can have a large influence on this ecosystem. What and how much we consume can tip the ecological balance in the intestine. A “western diet” containing mainly processed food will have a different effect on our health than a balanced diet fortified with pre- and probiotics. In recent years, new technologies have emerged, which made a more detailed understanding of microbial communities and ecosystems feasible. This includes progress in the sequencing of PCR-amplified phylogenetic marker genes as well as the collective microbial metagenome and metatranscriptome, allowing us to determine with an increasing level of detail, which microbial species are in the microbiota, understand what these microorganisms do and how they respond to changes in lifestyle and diet. These new technologies also include the use of synthetic and in vitro systems, which allow us to study the impact of substrates and addition of specific microbes to microbial communities at a high level of detail, and enable us to gather quantitative data for modelling purposes. Here, we will review the current state of microbiome research, summarizing the computational methodologies in this area and highlighting possible outcomes for personalized nutrition and medicine.

Description: Identification of new biomarkers of food and nutrient intake has developed fast over the past two decades and could potentially provide important new tools for compliance monitoring and dietary intake assessment in nutrition and health science. In recent years, metabolomics has played an important role in identifying a large number of putative biomarkers of food intake (BFIs). However, the large body of scientific literature on potential BFIs outside the metabolomics area should also be taken into account. In particular, we believe that extensive literature reviews should be conducted and that the quality of all suggested biomarkers should be systematically evaluated. In order to cover the literature on BFIs in the most appropriate and consistent manner, there is a need for appropriate guidelines on this topic. These guidelines should build upon guidelines in related areas of science while targeting the special needs of biomarker methodology. This document provides a guideline for conducting an extensive literature search on BFIs, which will provide the basis to systematically validate BFIs. This procedure will help to prioritize future work on the identification of new potential biomarkers and on validating these as well as other biomarker candidates, thereby providing better tools for future studies in nutrition and health.

Description: A large number of genome-wide association studies, transferability studies, and candidate gene studies performed in diverse populations around the world have identified gene variants that are associated with common human obesity. The mounting evidence suggests that these obesity gene variants interact with multiple environmental factors and increase susceptibility to this complex metabolic disease. The objective of this review article is to provide concise and updated information on energy balance, heritability of body weight, origins of gene variants, and gene-nutrient interactions in relation to human obesity. It is proposed that knowledge of these related topics will provide valuable insight for future preventative lifestyle intervention using targeted nutritional and medicinal therapies.

Description: Background The solute carrier family 30 member 8 gene ( SLC30A8 ) encodes a zinc transporter in the pancreatic beta cells and the major C-allele of a missense variant (rs13266634; C/T; R325W) in SLC30A8 is associated with an increased risk of type 2 diabetes (T2D). We hypothesized that the association between zinc intake and T2D may be modified by the SLC30A8 genotype. Results We carried out a prospective study among subjects with no history cardio-metabolic diseases in the Malmö Diet and Cancer Study cohort ( N  = 26,132, 38% men; 86% with genotype data). Zinc intake was assessed using a diet questionnaire and food record. During a median follow-up of 19 years, 3676 T2D cases occurred. A BMI-stratified Cox proportional hazards regression model with attained age as the time scale was used to model the association between total and dietary zinc intake, zinc supplement use, zinc to iron ratio, and risk of T2D adjusting for putative confounding factors. The median total zinc intake was 11.4 mg/day, and the median dietary zinc intake was 10.7 mg/day. Zinc supplement users (17%) had a median total zinc intake of 22.4 mg/day. Dietary zinc intake was associated with increased risk of T2D ( P trend  〈 0.0001). In contrast, we observed a lower risk of T2D among zinc supplement users (HR = 0.79, 95% CI 0.70–0.89). The SLC30A8 CC genotype was associated with a higher risk of T2D (HR = 1.16, 95% CI 1.07–1.24), and the effect was stronger among subjects with higher BMI ( P interaction  = 0.007). We observed no significant modification of the zinc-T2D associations by SLC30A8 genotype. However, a three-way interaction between SLC30A8 genotype, BMI, and zinc to iron ratio was observed ( P interaction  = 0.007). A high zinc to iron ratio conferred a protective associated effect on T2D risk among obese subjects, and the effect was significantly more pronounced among T-allele carriers. Conclusions Zinc supplementation and a high zinc to iron intake ratio may lower the risk of T2D, but these associations could be modified by obesity and the SLC30A8 genotype. The findings implicate that when considering zinc supplementation for T2D prevention, both obesity status and SLC30A8 genotype may need to be accounted for.

Description: Background Obesity is a complex pathology associated with dysbiosis, metabolic alterations, and low-grade chronic inflammation promoted by immune cells, infiltrating and populating the adipose tissue. Probiotic supplementation was suggested to be capable of counteracting obesity-associated immune and microbial alterations, based on its proven immunomodulatory activity and positive effect on gut microbial balance. Traditional fermented foods represent a natural source of live microbes, including environmental strains with probiotic features, which could transiently colonise the gut. The aim of our work was to evaluate the impact of supplementation with a complex foodborne bacterial consortium on obesity-associated inflammation and gut microbiota composition in a mouse model. Methods C57BL/6J mice fed a 45% high fat diet (HFD) for 90 days were supplemented with a mixture of foodborne lactic acid bacteria derived from the traditional fermented dairy product “Mozzarella di Bufala Campana” (MBC) or with the commercial probiotic GG strain of Lactobacillus rhamnosus (LGG). Inflammation was assessed in epididymal white adipose tissue (WAT) following HFD. Faecal microbiota composition was studied by next-generation sequencing. Results Significant reduction of epididymal WAT weight was observed in MBC-treated, as compared to LGG and control, animals. Serum metabolic profiling showed correspondingly reduced levels of triglycerides and higher levels of HDL cholesterol, as well as a trend toward reduction of LDL-cholesterol levels. Analysis of the principal leucocyte subpopulations in epididymal WAT revealed increased regulatory T cells and CD4 + cells in MBC microbiota-supplemented mice, as well as decreased macrophage and CD8 + cell numbers, suggesting anti-inflammatory effects. These results were associated with lower levels of pro-inflammatory cytokines and chemokines in WAT explants. Faecal bacterial profiling demonstrated increased Firmicutes / Bacteroidetes ratio in all mice groups following HFD. Conclusions Taken together, these results indicate a protective effect of MBC microbiota supplementation toward HFD-induced fat accumulation and triglyceride and cholesterol levels, as well as inflammation, suggesting a stronger effect of a mixed microbial consortium vs single-strain probiotic supplementation. The immunomodulatory activity exerted by the MBC microbiota could be due to synergistic interactions within the microbial consortium, highlighting the important role of dietary microbes with yet uncharacterised probiotic effect.

Description: Background Genetic polymorphisms of antioxidant enzymes CAT, GPX, and SOD are involved in the etiology of obesity and its principal comorbidities. The aim of the present study was to analyze the effect of aforementioned SNPs over the output of several variables in people with obesity after a nutritional intervention. The study included 92 Mexican women, which received a dietary intervention by 3 months. Participants were genotyped and stratified into two groups: (1) carriers; mutated homozygous plus heterozygous (CR) and (2) homozygous wild type (WT). A comparison between CR and WT was done in clinical (CV), biochemical (BV), and anthropometric variables (AV), at the beginning and at the end of the intervention. Results Participants ( n  = 92) showed statistically significant differences ( p  〈 0.05) at the end of the nutritional intervention in several CV, BV, and AV. However, two kinds of responses were observed after genotyping participants: (A) CR and WT showed statistically significant differences ( p  〈 0.05) in several CV, BV, and AV for the SNPs 599C〉T GPX1 (rs1050450), − 251A〉G SOD1 (rs2070424), and − 262C〉T CAT (rs1001179). (B) Only CR showed statistically changes ( p  〈 0.05) in several CV, BV, and AV for the SNPs − 21A〉T CAT (rs7943316) and 47C〉T SOD2 (rs4880). The dietary intervention effect was statistically significantly between the polymorphisms of 47C〉T SOD2 and BMI, SBP, TBARS, total cholesterol, and C-LCL ( p  〈 0.05) and between the polymorphisms of − 21A〉T CAT (rs7943316) and SBP, DBP, total cholesterol, and atherogenic index ( p  〈 0.05). Conclusion People with obesity display different response in several CV, BV, and AV after a nutritional intervention, depending on the antioxidant genetic background of SOD and CAT enzymes.

Description: Nutrigenetic research examines the effects of inter-individual differences in genotype on responses to nutrients and other food components, in the context of health and of nutrient requirements. A practical application of nutrigenetics is the use of personal genetic information to guide recommendations for dietary choices that are more efficacious at the individual or genetic subgroup level relative to generic dietary advice. Nutrigenetics is unregulated, with no defined standards, beyond some commercially adopted codes of practice. Only a few official nutrition-related professional bodies have embraced the subject, and, consequently, there is a lack of educational resources or guidance for implementation of the outcomes of nutrigenetic research. To avoid misuse and to protect the public, personalised nutrigenetic advice and information should be based on clear evidence of validity grounded in a careful and defensible interpretation of outcomes from nutrigenetic research studies. Evidence requirements are clearly stated and assessed within the context of state-of-the-art ‘evidence-based nutrition’. We have developed and present here a draft framework that can be used to assess the strength of the evidence for scientific validity of nutrigenetic knowledge and whether ‘actionable’. In addition, we propose that this framework be used as the basis for developing transparent and scientifically sound advice to the public based on nutrigenetic tests. We feel that although this area is still in its infancy, minimal guidelines are required. Though these guidelines are based on semi-quantitative data, they should stimulate debate on their utility. This framework will be revised biennially, as knowledge on the subject increases.

Description: Background Variation in the fat mass and obesity-associated gene ( FTO ) has been associated with susceptibility to obesity, but the association appears to be modified by diet. We investigated whether dietary protein intake modifies the association between FTO variant rs1558902 and body mass index (BMI) and waist circumference in young adults ( n  = 1491) from the cross-sectional Toronto Nutrigenomics and Health Study. Results Lifestyle, genetic, anthropometric, and biochemical data were collected and diet was assessed using a Toronto-modified Willett Food Frequency Questionnaire. General linear models stratified by ethnicity and adjusted for age, sex, and total energy intake were used to examine the association between FTO genotypes and measures of body weight, and whether protein intake modified any of the associations. East Asians who were homozygous for the rs1558902 risk allele (A) had a greater BMI ( p  = 0.004) and waist circumference ( p  = 0.03) than T allele carriers. This association was not observed in individuals of Caucasian or South Asian ancestry. Among East Asians, a significant FTO-protein interaction was observed for BMI ( p  = 0.01) and waist circumference ( p  = 0.007). Those with low protein intake (≤ 18% total energy intake) who were homozygous for the rs1558902 risk allele (A) had significantly higher BMI ( p  〈  0.0001) and waist circumference ( p  = 0.0006) compared to carriers of the T allele. These associations were absent in the high protein intake group (〉 18% total energy intake). Compared to Caucasians and South Asians, East Asians consumed a significantly higher ratio of animal-to-plant protein ( p  〈  0.05). Conclusions These findings suggest that high dietary protein intake may protect against the effects of risk variants in the FTO gene on BMI and waist circumference.

Description: Biomarkers are an efficient means to examine intakes or exposures and their biological effects and to assess system susceptibility. Aided by novel profiling technologies, the biomarker research field is undergoing rapid development and new putative biomarkers are continuously emerging in the scientific literature. However, the existing concepts for classification of biomarkers in the dietary and health area may be ambiguous, leading to uncertainty about their application. In order to better understand the potential of biomarkers and to communicate their use and application, it is imperative to have a solid scheme for biomarker classification that will provide a well-defined ontology for the field. In this manuscript, we provide an improved scheme for biomarker classification based on their intended use rather than the technology or outcomes (six subclasses are suggested: food compound intake biomarkers (FCIBs), food or food component intake biomarkers (FIBs), dietary pattern biomarkers (DPBs), food compound status biomarkers (FCSBs), effect biomarkers, physiological or health state biomarkers). The application of this scheme is described in detail for the dietary and health area and is compared with previous biomarker classification for this field of research.

Description: Background The inverse relationship between exercise capacity and its variation over time and both cardiovascular and all-cause mortality suggests the existence of an etiological nexus between cardiometabolic diseases and the molecular regulators of exercise capacity. Coordinated adaptive responses elicited by physical training enhance exercise performance and metabolic efficiency and possibly mediate the health benefits of physical exercise. In contrast, impaired expression of genes involved in mitochondrial biogenesis or protein turnover in skeletal muscle—key biological processes involved in adaptation to physical training—leads to insulin resistance and obesity. Ingestion of fructose has been shown to suppress the exercise-induced GLUT4 response in rat skeletal muscle. To evaluate in greater detail how fructose ingestion might blunt the benefits of physical training, we investigated the effects of fructose ingestion on exercise induction of genes that participate in regulation of mitochondrial biogenesis and protein turnover in rat’s skeletal muscle. Methods Eight-week-old Wistar rats were randomly assigned to sedentary (C), exercise (treadmill running)-only (E), fructose-only (F), and fructose + exercise (FE) groups and treated accordingly for 8 weeks. Blood and quadriceps femoris were collected for biochemistry, serum insulin, and gene expression analysis. Expression of genes involved in regulation of mitochondrial biogenesis and autophagy, GLUT4, and ubiquitin E3 ligases MuRF-1, and MAFbx/Atrogin-1 were assayed with quantitative real-time polymerase chain reaction. Results Aerobic training improved exercise capacity in both E and FE groups. A main effect of fructose ingestion on body weight and fasting serum triglyceride concentration was detected. Fructose ingestion impaired the expression of PGC-1α, FNDC5, NR4A3, GLUT4, Atg9, Lamp2, Ctsl, Murf-1, and MAFBx/Atrogin-1 in skeletal muscle of both sedentary and exercised animals while expression of Errα and Pparδ was impaired only in exercised rats. Conclusions Our results show that fructose ingestion impairs the expression of genes involved in biological processes relevant to exercise-induced remodeling of skeletal muscle. This might provide novel insight on how a dietary factor contributes to the genesis of disorders of glucose metabolism.

Description: Background A key feature of metabolic health is the ability to adapt upon dietary perturbations. A systemic review defined an optimal nutritional challenge test, the “PhenFlex test” (PFT). Recently, it has been shown that the PFT enables the quantification of all relevant metabolic processes involved in maintaining or regaining homeostasis of metabolic health. Furthermore, it was demonstrated that quantification of PFT response was more sensitive as compared to fasting markers in demonstrating reduced phenotypic flexibility in metabolically impaired type 2 diabetes subjects. Methods This study aims to demonstrate that quantification of PFT response can discriminate between different states of health within the healthy range of the population. Therefore, 100 healthy subjects were enrolled (50 males, 50 females) ranging in age (young, middle, old) and body fat percentage (low, medium, high), assuming variation in phenotypic flexibility. Biomarkers were selected to quantify main processes which characterize phenotypic flexibility in response to PFT: flexibility in glucose, lipid, amino acid and vitamin metabolism, and metabolic stress. Individual phenotypic flexibility was visualized using the “health space” by representing the four processes on the health space axes. By quantifying and presenting the study subjects in this space, individual phenotypic flexibility was visualized. Results Using the “health space” visualization, differences between groups as well as within groups from the healthy range of the population can be easily and intuitively assessed. The health space showed a different adaptation to the metabolic PhenFlex test in the extremes of the recruited population; persons of young age with low to normal fat percentage had a markedly different position in the health space as compared to persons from old age with normal to high fat percentage. Conclusion The results of the metabolic PhenFlex test in conjunction with the health space reliably assessed health on an individual basis. This quantification can be used in the future for personalized health quantification and advice.

Description: Background A key feature of metabolic health is the ability to adapt upon dietary perturbations. Recently, it was shown that metabolic challenge tests in combination with the new generation biomarkers allow the simultaneous quantification of major metabolic health processes. Currently, applied challenge tests are largely non-standardized. A systematic review defined an optimal nutritional challenge test, the “PhenFlex test” (PFT). This study aimed to prove that PFT modulates all relevant processes governing metabolic health thereby allowing to distinguish subjects with different metabolic health status. Therefore, 20 healthy and 20 type 2 diabetic (T2D) male subjects were challenged both by PFT and oral glucose tolerance test (OGTT). During the 8-h response time course, 132 parameters were quantified that report on 26 metabolic processes distributed over 7 organs (gut, liver, adipose, pancreas, vasculature, muscle, kidney) and systemic stress. Results In healthy subjects, 110 of the 132 parameters showed a time course response. Patients with T2D showed 18 parameters to be significantly different after overnight fasting compared to healthy subjects, while 58 parameters were different in the post-challenge time course after the PFT. This demonstrates the added value of PFT in distinguishing subjects with different health status. The OGTT and PFT response was highly comparable for glucose metabolism as identical amounts of glucose were present in both challenge tests. Yet the PFT reports on additional processes, including vasculature, systemic stress, and metabolic flexibility. Conclusion The PFT enables the quantification of all relevant metabolic processes involved in maintaining or regaining homeostasis of metabolic health. Studying both healthy subjects and subjects with impaired metabolic health showed that the PFT revealed new processes laying underneath health. This study provides the first evidence towards adopting the PFT as gold standard in nutrition research.

Description: Background Methionine, a central molecule in one-carbon metabolism, is an essential amino acid required for normal growth and development. Despite its importance to biological systems, methionine is toxic when administered at supra-physiological levels. The aim of this study was to investigate the effects of short-term methionine dietary modulation on the proximal jejunum, the section of the gut specifically responsible for amino acid absorption, in a mouse model. Eight-week-old CBA/J male mice were fed methionine-adequate (MAD; 6.5 g/kg) or methionine-supplemented (MSD; 19.5 g/kg) diets for 3.5 or 6 days (average food intake 100 g/kg body weight). The study design was developed in order to address the short-term effects of the methionine supplementation that corresponds to methionine dietary intake in Western populations. Biochemical indices in the blood as well as metabolic, epigenetic, transcriptomic, metagenomic, and histomorphological parameters in the gut were evaluated. Results By day 6, feeding mice with MSD (protein intake 〈10% different from MAD) resulted in increased plasma (2.3-fold; p  〈 0.054), but decreased proximal jejunum methionine concentrations (2.2-fold; p  〈 0.05) independently of the expression of neutral amino acid transporters. MSD has also caused small bowel bacteria colonization, increased the abundance of pathogenic bacterial species Burkholderiales and decreased the gene expression of the intestinal transmembrane proteins— Cldn8 (0.18-fold, p  〈 0.05), Cldn9 (0.24-fold, p  〈 0.01) and Cldn10 (0.05-fold, p  〈 0.05). Feeding MSD led to substantial histomorphological alterations in the proximal jejunum exhibited as a trend towards decreased plasma citrulline concentrations (1.8-fold, p  〈 0.07), as well as loss of crypt depth (by 28%, p  〈 0.05) and mucosal surface (by 20%, p  〈 0.001). Conclusions Together, these changes indicate that short-term feeding of MSD substantially alters the normal gut physiology. These effects may contribute to the pathogenesis of intestinal inflammatory diseases and/or sensitize the gut to exposure to other stressors.

Description: Background Vitamin B12 is an essential micronutrient in humans needed for health maintenance. Deficiency of vitamin B12 has been linked to dietary, environmental and genetic factors. Evidence for the genetic basis of vitamin B12 status is poorly understood. However, advancements in genomic techniques have increased the knowledge-base of the genetics of vitamin B12 status. Based on the candidate gene and genome-wide association (GWA) studies, associations between genetic loci in several genes involved in vitamin B12 metabolism have been identified. Objective The objective of this literature review was to identify and discuss reports of associations between single-nucleotide polymorphisms (SNPs) in vitamin B12 pathway genes and their influence on the circulating levels of vitamin B12. Methods Relevant articles were obtained through a literature search on PubMed through to May 2017. An article was included if it examined an association of a SNP with serum or plasma vitamin B12 concentration. Beta coefficients and odds ratios were used to describe the strength of an association, and a P  〈 0.05 was considered as statistically significant. Two reviewers independently evaluated the eligibility for the inclusion criteria and extracted the data. Results From 23 studies which fulfilled the selection criteria, 16 studies identified SNPs that showed statistically significant associations with vitamin B12 concentrations. Fifty-nine vitamin B12-related gene polymorphisms associated with vitamin B12 status were identified in total, from the following populations: African American, Brazilian, Canadian, Chinese, Danish, English, European ancestry, Icelandic, Indian, Italian, Latino, Northern Irish, Portuguese and residents of the USA. Conclusion Overall, the data analyzed suggests that ethnic-specific associations are involved in the genetic determination of vitamin B12 concentrations. However, despite recent success in genetic studies, the majority of identified genes that could explain variation in vitamin B12 concentrations were from Caucasian populations. Further research utilizing larger sample sizes of non-Caucasian populations is necessary in order to better understand these ethnic-specific associations.

Description: Background Obesity, a major cause of death and disability, is increasing worldwide. Obesity is characterized by a chronic, low-grade inflammatory state which is suggested to play a critical role in the development of obesity-related diseases like cardiovascular diseases and type 2 diabetes. In fact, in the hours following consumption of a meal, a transient increase in inflammatory markers occurs, a response that is exaggerated in obese subjects. Dietary composition, including content of dietary fatty acids, may affect this inflammatory response both acutely and chronically, and thereby be predictive of progression of disease. The aim of the review was to summarize the literature from 2010 to 2016 regarding the effects of dietary fat intake on levels of inflammatory markers in overweight and obesity in human randomized controlled trials. Methods and results We performed a literature search in MEDLINE, EMBASE, and PubMed databases. The literature search included human randomized controlled trials, both postprandial and long-term interventions, from January 2010 to September 2016. In total, 37 articles were included. Interventions with dairy products, vegetable oils, or nuts showed minor effects on inflammatory markers. The most consistent inflammatory-mediating effects were found in intervention with whole diets, which suggests that many components of the diet reduce inflammation synergistically. Furthermore, interventions with weight reduction and different fatty acids did not clearly show beneficial effects on inflammatory markers. Conclusion Most interventions showed either no or minor effects of dietary fat intake on inflammatory markers in overweight and obese subjects. To progress our understanding on how diet and dietary components affect our health, mechanistic studies are required. Hence, future studies should include whole diets and characterization of obese phenotypes at a molecular level, including omics data and gut microbiota.

Description: Background We investigated whether the long-term consumption of a symbiotic formulation with Lactobacillus fermentum (probiotic) and β-glucan from cauliflower mushroom (prebiotic) would delay the progression of post-menopausal symptoms in ovariectomized (OVX) rats and explored their mechanisms of action, including changes in gut microbiota. Methods OVX rats were fed with high-fat diets containing 1% dextrin (control), 1% lyophilized cauliflower mushroom extract (CFM), 0.1% L . fermentum JS (LFE), 1% CFM plus 0.1% LFE (CFLF), or 30 μg 17β-estradiol/kg body weight (positive-control) for 8 weeks. Results CFM contained 95.8% β-glucans. OVX increased the ratio of Firmicutes and Bacteroidetes in the large intestines. Only CFLF lowered tail skin temperature without increasing serum 17β-estradiol and uterine index. Visceral fat mass was lower in CFLF and positive-control groups by increasing daily energy expenditure and fat oxidation. Dyslipidemia induced by OVX was improved by CFM and CFLF as much as in the positive-control group. Homeostasis model assessment estimate of insulin resistance was lower in CFLF than in the positive-control. Hepatic insulin signaling (pAkt➔GSK-3β) was potentiated in the ascending order of the control, LFE, CFM, CFLF, and positive-control. AMPK phosphorylation showed similar patterns of hepatic insulin signaling but LFE increased it more than CFM. The changes in gut microbiota were prevented by CFLF in OVX rats, and the ratio of Firmicutes and Bacteroidetes in the CFLF was similar to the positive-control group. Conclusion OVX changed gut microbiota and was associated with menopausal symptoms; however, the synbiotics, CFM and LFE, prevented menopausal symptoms and improved the gut microbiota in estrogen-deficient rats.

Description: Background During evolution, humans colonized different ecological niches and adopted a variety of subsistence strategies that gave rise to diverse selective pressures acting across the genome. Environmentally induced selection of vitamin, mineral, or other cofactor transporters could influence micronutrient-requiring molecular reactions and contribute to inter-individual variability in response to foods and nutritional interventions. Methods A comprehensive list of genes coding for transporters of cofactors or their precursors was built using data mining procedures from the HGDP dataset and then explored to detect evidence of positive genetic selection. This dataset was chosen since it comprises several genetically diverse worldwide populations whom ancestries have evolved in different environments and thus lived following various nutritional habits and lifestyles. Results We identified 312 cofactor transporter (CT) genes involved in between-cell or sub-cellular compartment distribution of 28 cofactors derived from dietary intake. Twenty-four SNPs distributed across 14 CT genes separated populations into continental and intra-continental groups such as African hunter-gatherers and farmers, and between Native American sub-populations. Notably, four SNPs were located in SLC24A3 with one being a known eQTL of the NCKX3 protein. Conclusions These findings could support the importance of considering individual’s genetic makeup along with their metabolic profile when tailoring personalized dietary interventions for optimizing health.

Description: In the dietary and health research area, biomarkers are extensively used for multiple purposes. These include biomarkers of dietary intake and nutrient status, biomarkers used to measure the biological effects of specific dietary components, and biomarkers to assess the effects of diet on health. The implementation of biomarkers in nutritional research will be important to improve measurements of dietary intake, exposure to specific dietary components, and of compliance to dietary interventions. Biomarkers could also help with improved characterization of nutritional status in study volunteers and to provide much mechanistic insight into the effects of food components and diets. Although hundreds of papers in nutrition are published annually, there is no current ontology for the area, no generally accepted classification terminology for biomarkers in nutrition and health, no systematic validation scheme for these biomarker classes, and no recent systematic review of all proposed biomarkers for food intake. While advanced databases exist for the human and food metabolomes, additional tools are needed to curate and evaluate current data on dietary and health biomarkers. The Food Biomarkers Alliance (FoodBAll) under the Joint Programming Initiative—A Healthy Diet for a Healthy Life (JPI-HDHL)—is aimed at meeting some of these challenges, identifying new dietary biomarkers, and producing new databases and review papers on biomarkers for nutritional research. This current paper outlines the needs and serves as an introduction to this thematic issue of Genes & Nutrition on dietary and health biomarkers.

Description: Dietary supplementation of essential amino acids (EAAs) has been shown to promote healthspan. EAAs regulate, in fact, glucose and lipid metabolism and energy balance, increase mitochondrial biogenesis, and maintain immune homeostasis. Basic science and epidemiological results indicate that dietary macronutrient composition affects healthspan through multiple and integrated mechanisms, and their effects are closely related to the metabolic status to which they act. In particular, EAA supplementation can trigger different and even opposite effects depending on the catabolic and anabolic states of the organisms. Among others, gut-associated microbial communities (referred to as gut microbiota) emerged as a major regulator of the host metabolism. Diet and host health influence gut microbiota, and composition of gut microbiota, in turn, controls many aspects of host health, including nutrient metabolism, resistance to infection, and immune signals. Altered communication between the innate immune system and the gut microbiota might contribute to complex diseases. Furthermore, gut microbiota and its impact to host health change largely during different life phases such as lactation, weaning, and aging. Here we will review the accumulating body of knowledge on the impact of dietary EAA supplementation on the host metabolic health and healthspan from a holistic perspective. Moreover, we will focus on the current efforts to establish causal relationships among dietary EAAs, gut microbiota, and health during human development.

Description: In recent years, the link between regulatory microRNAs (miRNAs) and diseases has been the object of intensive research. miRNAs have emerged as key mediators of metabolic processes, playing crucial roles in maintaining/altering physiological processes, including energy balance and metabolic homeostasis. Altered miRNAs expression has been reported in association with obesity, both in animal and human studies. Dysregulation of miRNAs may affect the status and functions of different tissues and organs, including the adipose tissue, pancreas, liver, and muscle, possibly contributing to metabolic abnormalities associated with obesity and obesity-related diseases. More recently, the discovery of circulating miRNAs easily detectable in plasma and other body fluids has emphasized their potential as both endocrine signaling molecules and disease indicators. In this review, the status of current research on the role of miRNAs in obesity and related metabolic abnormalities is summarized and discussed.

Description: Background High-intensity exercise induces many metabolic responses. In is unknown whether the response in the peripheral blood mononuclear cells (PBMCs) reflects the response in skeletal muscle and whether mRNA expression after exercise can be modulated by nutritional intake. The aims were to (i) investigate the effect of dairy proteins on acute responses to exercise in skeletal muscle and PBMCs measuring gene expression and (ii) compare this response in young and older subjects. Methods We performed two separate studies in young (20–40 years) and older subjects (≥70 years). Subjects were randomly allocated to a milk group or a whey group. Supplements were provided immediately after a standardized exercise session. We measured mRNA expression of selected genes after a standardized breakfast and 60/120 min after finishing the exercise, using RT-qPCR. Results We observed no significant differences in mRNA expression between the milk and the whey group; thus, we merged both groups for further analysis. The mRNA expression of IL6 , TNF , and CCL2 in skeletal muscle increased significantly after exercise compared with smaller or no increase, in mRNA expression in PBMCs in all participants. The mRNA expression of IL1RN , IL8 , and IL10 increased significantly in skeletal muscle and PBMCs. Some mRNA transcripts were differently regulated in older compared to younger participants in PBMCs. Conclusions An acute bout of heavy-load strength exercise, followed by protein supplementation, caused overlapping, but also unique, responses in skeletal muscle and PBMCs, suggesting tissue-specific functions in response to exercise. However, no different effects of the different protein supplements were observed. Altered mRNA expressions in PBMCs of older participants may affect regenerative mechanisms.

Description: Background The dietary xanthophylls, lutein and zeaxanthin, accumulate in primate retina and brain, and emerging evidence indicates neural lutein content may be beneficial for cognition. Neural xanthophyll content in primates varies greatly among individuals, and genetic factors are likely to be significant contributors. Subspecies of rhesus macaques originating from different geographic locations are known to differ genetically, but the effect of origin on gene expression and carotenoid status has not been determined. The study objective was to determine whether xanthophyll status and expression of carotenoid-related genes, as well as genes with known variants between subspecies, differ between the brains of adult rhesus monkeys of Indian and Chinese origin. Methods Samples of prefrontal cortex, cerebellum, and striatum were collected from adult monkeys ( n  = 9) fed a standard stock diet containing carotenoids. Serum and brain carotenoids were determined using reverse-phase high-performance liquid chromatography. For each brain region, RNA sequencing and real-time quantitative polymerase chain reaction were used to determine differentially expressed genes between the subspecies. Results Indian-origin monkeys had higher xanthophyll levels in brain tissue compared to Chinese-origin monkeys despite consuming similar amounts of dietary carotenoids. In a region-specific manner, four genes related to carotenoid and fatty acid metabolism ( BCO2 , RPE65 , ELOVL4 , FADS2 ) and four genes involved in the immune response ( CD4 , CD74 , CXCL12 LTBR ) were differentially expressed between Indian- and Chinese-origin monkeys. Expression of all four genes involved in carotenoid and fatty acid metabolism were correlated with brain xanthophyll concentration in a region-specific manner. Conclusions These results indicate that origin is related to differences in both gene expression and xanthophyll content in the brain. Findings from this study may have important implications regarding genetic diversity, lutein status, and cognition in primates.

Description: Background Vitamins and carotenoids are key micronutrients facilitating the maintenance of health, as evidenced by the increased risk of disease with low intake. Optimal phenotypic flexibility, i.e., the ability to respond to a physiological challenge, is an essential indicator of health status. Therefore, health can be measured by applying a challenge test and monitoring the response of relevant phenotypic processes. In this study, we assessed the correlation of three fat-soluble vitamins, (i.e., vitamin A or retinol, vitamin D 3 , two homologues of vitamin E) and four carotenoids (i.e., α-carotene, β-carotene, β-cryptoxanthin, and lycopene), with characteristics of metabolic and inflammatory parameters at baseline and in response to a nutritional challenge test (NCT) in a group of 36 overweight and obese male subjects, using proteomics and metabolomics platforms. The phenotypic flexibility concept implies that health can be measured by the ability to adapt to a NCT, which may offer a more sensitive way to assess changes in health status of healthy subjects. Results Correlation analyses of results after overnight fasting revealed a rather evenly distributed network in a number of relatively strong correlations per micronutrient, with minor overlap between correlation profiles of each compound. Correlation analyses of challenge response profiles for metabolite and protein parameters with micronutrient status revealed a network that is more skewed towards α-carotene and γ-tocopherol suggesting a more prominent role for these micronutrients in the maintenance of phenotypic flexibility. Comparison of the networks revealed that there is merely overlap of two parameters (inositol and oleic acid (C18:1)) affirming that there is a specific biomarker response profile upon NCT. Conclusions Our study shows that applying the challenge test concept is able to reveal previously unidentified correlations between specific micronutrients and health-related processes, with potential relevance for maintenance of health that were not observed by correlating homeostatic measurements. This approach will contribute to insights on the influence of micronutrients on health and help to create efficient micronutrient intervention programs.

Description: Background To elucidate the effects of altered dietary carbohydrate and fat balance on liver and adipose tissue transcriptomes, 3-week-old rats were fed three kinds of diets: low-, moderate-, and high-fat diets (L, M, and H) containing a different ratio of carbohydrate-fat (C-F) (65:15, 60:20, and 35:45 in energy percent, respectively). Methods The rats consumed the diets for 9 weeks and were subjected to biochemical and DNA microarray analyses. Results The rats in the H-group exhibited lower serum triacylglycerol (TG) levels but higher liver TG and cholesterol content than rats in the L-group. The analysis of differentially expressed genes (DEGs) between each group (L vs M, M vs H, and L vs H) in the liver revealed about 35% of L vs H DEGs that were regulated in the same way as M vs H DEGs, and most of the others were L- vs H-specific. Gene ontology analysis of these L vs H DEGs indicated that those related to fatty acid synthesis and circadian rhythm were enriched. Interestingly, about 30% of L vs M DEGs were regulated in a reverse way compared with L vs H and M vs H DEGs. These reversed liver DEGs included M-up/H-down genes ( Sds for gluconeogenesis from amino acids) and M-down/H-up genes ( Gpd2 for gluconeogenesis from glycerol, Agpat9 for TG synthesis, and Acot1 for beta-oxidation). We also analyzed L vs H DEGs in white (WAT) and brown (BAT) adipose tissues and found that both oxidation and synthesis of fatty acids were inhibited in these tissues. Conclusions These results indicate that the alteration of dietary C-F balance differentially affects the transcriptomes of metabolizing and energy-storing tissues.

Description: Background Gene expression profiles of intestinal mucosa of chickens and pigs fed over long-term periods (days/weeks) with a diet rich in rye and a diet supplemented with zinc, respectively, or of chickens after a one-day amoxicillin treatment of chickens, were recorded recently. Such dietary interventions are frequently used to modulate animal performance or therapeutically for monogastric livestock. In this study, changes in gene expression induced by these three interventions in cultured “Intestinal Porcine Epithelial Cells” (IPEC-J2) recorded after a short-term period of 2 and 6 hours, were compared to the in vivo gene expression profiles in order to evaluate the capability of this in vitro bioassay in predicting in vivo responses. Methods Lists of response genes were analysed with bioinformatics programs to identify common biological pathways induced in vivo as well as in vitro. Furthermore, overlapping genes and pathways were evaluated for possible involvement in the biological processes induced in vivo by datamining and consulting literature. Results For all three interventions, only a limited number of identical genes and a few common biological processes/pathways were found to be affected by the respective interventions. However, several enterocyte-specific regulatory and secreted effector proteins that responded in vitro could be related to processes regulated in vivo, i.e. processes related to mineral absorption, (epithelial) cell adherence and tight junction formation for zinc, microtubule and cytoskeleton integrity for amoxicillin, and cell-cycle progression and mucus production for rye. Conclusions Short-term gene expression responses to dietary interventions as measured in the in vitro bioassay have a low predictability for long-term responses as measured in the intestinal mucosa in vivo. The short-term responses of a set regulatory and effector genes, as measured in this bioassay, however, provided additional insight into how specific processes in piglets and broilers may be modulated by “early” signalling molecules produced by enterocytes. The relevance of this set of regulatory/effector genes and cognate biological processes for zinc deficiency and supplementation, gluten allergy (rye), and amoxicillin administration in humans is discussed.

Description: Background Epidemiological studies suggest that hyponutrition during the fetal period increases the risk of mental disorders such as attention deficit hyperactivity disorder and autism-spectrum disorder, which has been experimentally supported using animal models. However, previous experimental hyponutrition or protein-restricted (PR) diets affected stages other than the fetal stage, such as formation of the egg before insemination, milk composition during lactation, and maternal nursing behavior. Results We conducted in vitro fertilization and embryo transfer in mice and allowed PR diet and folic acid-supplemented PR diet to affect only fetal environments. Comprehensive phenotyping of PR and control-diet progenies showed moderate differences in fear/anxiety-like, novelty-seeking, and prosocial behaviors, irrespective of folic-acid supplementation. Changes were also detected in gene expression and genomic methylation in the brain. Conclusions These results suggest that epigenetic factors in the embryo/fetus influence behavioral and epigenetic phenotypes of progenies. Significant epigenetic alterations in the brains of the progenies induced by the maternal-protein restriction were observed in the present study. To our knowledge, this is first study to evaluate the effect of maternal hyponutrition on behavioral phenotypes using reproductive technology.

Description: Androgens, the main male sex steroids, are the critical factors responsible for the development of the male phenotype during embryogenesis and for the achievement of sexual maturation and puberty. In adulthood, androgens remain essential for the maintenance of male reproductive function and behavior. Androgens, acting through the androgen receptor (AR), regulate male sexual differentiation during development, sperm production beginning from puberty, and maintenance of prostate homeostasis. Several substances present in the environment, now classified as endocrine disruptors (EDCs), strongly interfere with androgen actions in reproductive and non-reproductive tissues. EDCs are a heterogeneous group of xenobiotics which include synthetic chemicals used as industrial solvents/lubricants, plasticizers, additives, agrochemicals, pharmaceutical agents, and polyphenols of plant origin. These compounds are even present in the food as components (polyphenols) or food/water contaminants (pesticides, plasticizers used as food packaging) rendering the diet as the main route of exposure to EDCs for humans. Although huge amount of literature reports the (anti)estrogenic effects of different EDCs, relatively scarce information is available on the (anti)androgenic effects of EDCs. Here, the effects and mechanism of action of phytochemicals and pesticides and plasticizers as possible modulators of AR activities will be reviewed taking into account that insight derived from principles of endocrinology are required to estimate EDC consequences on endocrine deregulation and disease.

Description: Background Inflammation plays a central role in chronic diseases occurring in the contemporary society. The health benefits of omega-3 (n-3) fatty acids (FAs), mostly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been reported. However, their mechanisms of action are poorly understood. We explored dose and time effects of EPA, DHA, and a mixture of EPA + DHA on the expression of inflammatory genes in stimulated macrophages. Methods Lipopolysaccharide was used to stimulate human THP-1 macrophages. Cells were incubated in different conditions in the presence of n-3 FAs and LPS, and mRNA levels of inflammatory genes were measured by real-time PCR. Cytokine levels in culture media were measured. Results The mixture of EPA + DHA had a more effective inhibitory effect than either DHA or EPA alone, DHA being more potent than EPA. For both EPA and DHA, 75 μM of FAs had a more important anti-inflammatory effect than 10 or 50 μM. For gene expression, EPA had the greater action during the post-incubation (after LPS treatment) condition while DHA and EPA + DHA were more potent during the co-incubation (n-3 FAs and LPS). Cytokine concentrations decreased more markedly in the co-incubation condition. Conclusions These results suggest that in stimulated macrophages, expression levels of genes involved in inflammation are influenced by the dose, the type of n-3 FAs, and the time of incubation.

Description: Background Hepatic fatty acids (FAs) are modified through different metabolic pathways including elongation and desaturation. These processes are catalyzed by elongases and desaturases, respectively. Glucose, by transcription factors, regulates these processes. The aim of the study was to evaluate the influence of high carbohydrate diet (68%) on the expression of elongase (Elovl-2, Elovl-5, and Elovl-6) and desaturase (∆5D, ∆6D, Scd 1, Scd 2) genes and the activity of the enzymes. The changes in serum lipid profile (triglycerides (TG), total cholesterol (TC), HDL cholesterol) and glucose concentration were measured. Male Wistar rats were randomized into two study groups: animals fed with high carbohydrate diet ( n  = 6; HiCHO) and a control group fed with a standard diet ( n  = 6; ST). The expression of mRNA was determinate using reverse transcription PCR (RT-PCR). Hepatic FA composition was determined by gas chromatography, and FA ratios were used to estimate the activity of enzymes. Serum lipid profile and glucose concentration were measured using spectrophotometric methods. Results The mean values of transcript expression of all examined elongases and desaturases in liver HiCHO rats were higher as compared to ST. Higher expression did not always correspond to higher activity (as index). More monounsaturated FAs (MUFAs) were detected in the liver of HiCHO rats as compared to ST. Serum TG level was higher in the HiCHO than in ST. Conclusions These studies support the notion that the regulation of both Elovl and desaturase expression may play an important role in managing hepatic lipid composition in response to changes in dietary status.

Description: The complex physiology of living organisms represents a challenge for mechanistic understanding of the action of dietary bioactives in the human body and of their possible role in health and disease. Animal, cell, and microbial models have been extensively used to address questions that could not be pursued experimentally in humans, posing an additional level of complexity in translation of the results to healthy and diseased metabolism. The past few decades have witnessed a surge in development of increasingly sensitive molecular techniques and bioinformatic tools for storing, managing, and analyzing increasingly large datasets. Application of such powerful means to molecular nutrition research led to a major leap in study designs and experimental approaches yielding experimental data connecting dietary components to human health. Scientific journals bear major responsibilities in the advancement of science. As primary actors of dissemination to the scientific community, journals can impose rigid criteria for publishing only sound, reliable, and reproducible data. Journal policies are meant to guide potential authors to adopt the most updated standardization guidelines and shared best practices. Such policies evolve in parallel with the evolution of novel approaches and emerging challenges and therefore require constant updating. We highlight in this manuscript the major scientific issues that led to formulating new, updated journal policies for Genes & Nutrition , a journal which targets the growing field of nutritional systems biology interfacing personalized nutrition and preventive medicine, with the ultimate goal of promoting health and preventing or treating disease. We focus here on relevant issues requiring standardization in nutrition research. We also introduce new sections on human genetic variation and nutritional bioinformatics which follow the evolution of nutritional science into the twenty-first century.

Description: Background The level of omega-6 and omega-3 polyunsaturated fatty acids can affect many cellular systems and function via nuclear receptors or the bioactive lipid regulation of gene expression. The objective of this study was to investigate changes in the muscle transcriptome and the biological functions regulated by increased consumption of omega-3 and omega-6 fatty acids in the pig gluteus medius muscle. Results The transcriptome of the gluteus medius muscle was studied for pigs subjected to either a control diet or a diet supplemented with linseed and rapeseed oil to increase polyunsaturated fatty acid content. Next-generation sequencing (NGS) was used to generate the muscle tissue transcriptome database pointing differentially expressed genes (DEG). Comparative expression analyses identified 749 genes significantly differing at least in the twofold of change between two groups of animals fed with divergent level of omega-3 and omega-6 fatty acids. The expression of 219 genes was upregulated, and the expression of 530 genes was downregulated in the group of pigs supplemented with omega-3 and omega-6 fatty acids in relation to control group pigs. Results of RNA-seq indicated a role of fatty acid in the regulation of the expression of genes which are essential for muscle tissue development and functioning. Functional analysis revealed that the identified genes were important for a number of biological processes including inflammatory response, signaling, lipid metabolism, and homeostasis. Conclusions Summarizing, obtained results provide strong evidence that omega-6 and omega-3 fatty acids regulate fundamental metabolic processes in muscle tissue development and functioning.

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: 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: 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: Background Non-celiac wheat sensitivity is an emerging wheat-related syndrome showing peak prevalence in Western populations. Recent studies hypothesize that new gliadin alleles introduced in the human diet by replacement of ancient wheat with modern varieties can prompt immune responses mediated by the CXCR3-chemokine axis potentially underlying such pathogenic inflammation. This cultural shift may also explain disease epidemiology, having turned European-specific adaptive alleles previously targeted by natural selection into disadvantageous ones. Methods To explore this evolutionary scenario, we performed ultra-deep sequencing of genes pivotal in the CXCR3-inflammatory pathway on individuals diagnosed for non-celiac wheat sensitivity and we applied anthropological evolutionary genetics methods to sequence data from worldwide populations to investigate the genetic legacy of natural selection on these loci. Results Our results indicate that balancing selection has maintained two divergent CXCL10/CXCL11 haplotypes in Europeans, one responsible for boosting inflammatory reactions and another for encoding moderate chemokine expression. Conclusions This led to considerably higher occurrence of the former haplotype in Western people than in Africans and East Asians, suggesting that they might be more prone to side effects related to the consumption of modern wheat varieties. Accordingly, this study contributed to shed new light on some of the mechanisms potentially involved in the disease etiology and on the evolutionary bases of its present-day epidemiological patterns. Moreover, overrepresentation of disease homozygotes for the dis-adaptive haplotype plausibly accounts for their even more enhanced CXCR3-axis expression and for their further increase in disease risk, representing a promising finding to be validated by larger follow-up studies.

Description: Background Considering that vitamin A deficiency modulates hepcidin expression and consequently affects iron metabolism, we evaluated the effect of vitamin A deficiency in the expression of genes involved in the hemojuvelin (HJV)-bone morphogenetic protein 6 (BMP6)-small mothers against decapentaplegic protein (SMAD) signaling pathway. Methods Male Wistar rats were treated: control AIN-93G diet (CT), vitamin A-deficient diet (VAD), iron-deficient diet (FeD), vitamin A- and iron-deficient diet (VAFeD), or 12 mg all- trans retinoic acid (atRA)/kg diet. Results Vitamin A deficiency (VAD) increased hepatic Bmp6 and Hfe2 mRNA levels and down-regulated hepatic Hamp , Smad7 , Rarα , and intestinal Fpn1 mRNA levels compared with the control. The FeD rats showed lower hepatic Hamp , Bmp6 , and Smad7 mRNA levels compared with those of the control, while in the VAFeD rats only Hamp and Smad7 mRNA levels were lower than those of the control. The VAFeD diet up-regulated intestinal Dmt1 mRNA levels in relation to those of the control. The replacement of retinyl ester by atRA did not restore hepatic Hamp mRNA levels; however, the hepatic Hfe2 , Bmp6 , and Smad7 mRNA levels were similar to the control. The atRA rats showed an increase of hepatic Rarα mRNA levels and a reduction of intestinal Dmt1 mRNA and Fpn1 levels compared with those of the control. Conclusions The HJV-BMP6-SMAD signaling pathway that normally activates the expression of hepcidin in iron deficiency is impaired by vitamin A deficiency despite increased expression of liver Bmp6 and Hfe2 mRNA levels and decreased expression of Smad7 mRNA. This response may be associated to the systemic iron deficiency and spleen iron retention promoted by vitamin A deficiency.

Description: Background Almost all animals adapt to dietary restriction through alternative life history traits that affect their growth, reproduction, and survival. Economized management of fat stores is a prevalent type of such adaptations. Because one-carbon metabolism is a critical gauge of food availability, in this study, we used Caenorhabditis elegans to test whether the methyl group donor choline regulates adaptive responses to dietary restriction. We used a modest dietary restriction regimen that prolonged the fecund period without reducing the lifetime production of progeny, which is the best measure of fitness. Results We found that dietary supplementation with choline abrogate the dietary restriction-induced prolongation of the reproductive period as well as the accumulation and delayed depletion of large lipid droplets and whole-fat stores and increased the survival rate in the cold. By contrast, the life span-prolonging effect of dietary restriction is not affected by choline. Moreover, we found that dietary restriction led to the enlargement of lipid droplets within embryos and enhancement of the cold tolerance of the progeny of dietarily restricted mothers. Both of these transgenerational responses to maternal dietary restriction were abrogated by exposing the parental generation to choline. Conclusions In conclusion, supplementation with the methyl group donor choline abrogates distinct responses to dietary restriction related to reproduction, utilization of fat stored in large lipid droplets, cold tolerance, and thrifty phenotypes in C. elegans .

Description: Background Menopausal symptoms are associated with inflammation. Curcumin is a well-known anti-inflammatory bioactive compound from turmeric whereas tetrahydrocurcumin (THC) is a major metabolite of curcumin that may have different efficacies. However, they have not been studied for anti-menopausal symptoms and anti-osteoarthritis effects. We compared the efficacies of curcumin and THC for preventing postmenopausal and osteoarthritis symptoms in ovariectomized (OVX) obese rats with monoiodoacetate (MIA) injections into the right knee to generate a similar pathology as osteoarthritis. Methods OVX rats were provided a 45 % fat diet containing either (1) 0.4 % curcumin (curcumin), (2) 0.4 % THC, (3) 30 μg/kg body weight 17β-estradiol + 0.4 % dextrin (positive control), (4) 0.4 % dextrin (placebo; control), or (5) 0.4 % dextrin with no MIA injection (normal control) for 4 weeks. At the beginning of the fifth week, OVX rats were given articular injections of MIA or normal-control saline into the right knee and the assigned diets were provided for an additional 3 weeks. Results Curcumin and THC had similar efficacies for skin tail temperature in OVX rats whereas THC, but not curcumin, prevented glucose intolerance, which might be involved in exacerbating osteoarthritis. Both protected against osteoarthritis symptoms and pain-related behaviors better than 17β-estradiol treatment in estrogen-deficient rats. Curcumin and THC prevented the deterioration of articular cartilage compared to control. They also maintained lean body mass and lowered fat mass as much as 17β-estradiol treatment. The improvement in osteoarthritis symptoms was associated with decreased gene expressions of matrix metalloproteinase ( MMP ) 3 and MMP13 and tumor necrosis factor-α, interleukin ( IL ) 1β , and IL6 in the articular cartilage. Conclusions THC and curcumin are effective for treating postmenopausal and osteoarthritis symptoms in OVX rats with MIA-induced osteoarthritis-like symptoms and may have potential as interventions for menopausal and osteoarthritic symptoms in humans.

Description: Background Adult skeletal muscle myogenesis depends on the activation of satellite cells that have the potential to differentiate into new fibers. Gamma-oryzanol (GO), a commercially available nutriactive phytochemical, has gained global interest on account of its muscle-building and regenerating effects. Here, we investigated GO for its potential influence on myogenesis, using equine satellite cell culture model, since the horse is a unique animal, bred and exercised for competitive sport. To our knowledge, this is the first report where the global gene expression in cultured equine satellite cells has been described. Methods Equine satellite cells were isolated from semitendinosus muscle and cultured until the second day of differentiation. Differentiating cells were incubated with GO for the next 24 h. Subsequently, total RNA from GO-treated and control cells was isolated, amplified, labeled, and hybridized to two-color Horse Gene Expression Microarray slides. Quantitative PCR was used for the validation of microarray data. Results Our results revealed 58 genes with changed expression in GO-treated vs. control cells. Analysis of expression changes suggests that various processes are reinforced by GO in differentiating equine satellite cells, including inhibition of myoblast differentiation, increased proliferation and differentiation, stress response, and increased myogenic lineage commitment. Conclusions The present study may confirm putative muscle-enhancing abilities of GO; however, the collective role of GO in skeletal myogenesis remains equivocal. The diversity of these changes is likely due to heterogenous growth rate of cells in primary culture. Genes identified in our study, modulated by the presence of GO, may become potential targets of future research investigating impact of this supplement in skeletal muscle on proteomic and biochemical level.

Description: Background Diet has a great impact on the risk of developing features of metabolic syndrome (MetS), type 2 diabetes mellitus (T2DM), and cardiovascular diseases (CVD). We evaluated whether a long-term healthy Nordic diet (ND) can modify the expression of inflammation and lipid metabolism-related genes in peripheral blood mononuclear cells (PBMCs) during a 2-h oral glucose tolerance test (OGTT) in individuals with MetS. Methods A Nordic multicenter randomized dietary study included subjects ( n  = 213) with MetS, randomized to a ND group or a control diet (CD) group applying an isocaloric study protocol. In this sub-study, we included subjects ( n  = 89) from three Nordic centers: Kuopio ( n  = 26), Lund ( n  = 30), and Oulu ( n  = 33) with a maximum weight change of ±4 kg, high-sensitivity C-reactive protein concentration ≤10 mg L −1 , and baseline body mass index 〈39 kg m −2 . PBMCs were isolated, and the mRNA gene expression analysis was measured by quantitative real-time polymerase chain reaction (qPCR). We analyzed the mRNA expression changes of 44 genes before and after a 2hOGTT at the beginning and the end of the intervention. Results The healthy ND significantly down-regulated the expression of toll-like receptor 4 ( TLR4 ), interleukin 18 ( IL18 ), and thrombospondin receptor ( CD36 ) mRNA transcripts and significantly up-regulated the expression of peroxisome proliferator-activated receptor delta ( PPARD ) mRNA transcript after the 2hOGTT compared to the CD. Conclusions A healthy ND is able to modify the gene expression in PBMCs after a 2hOGTT. However, more studies are needed to clarify the biological and clinical relevance of these findings.

Description: Background Emerging evidence suggests beneficial effects of omega-3 fatty acids on diabetic complications. The present study compared the progressive effects of metformin and flax/fish oil on lipid metabolism, inflammatory markers, and liver and renal function test markers in streptozotocin-nicotinamide-induced diabetic rats. Methods Streptozotocin-induced diabetic rats were randomized into control and four diabetic groups: streptozotocin (STZ), metformin (200 mg/kg body weight (b.w)/day (D)), flax and fish oil (500 mg/kg b.w/D). Results Metformin and flax and fish oil exhibited increased expression of transcription factor peroxisome proliferator-activated receptor γ while the treatment downregulated sterol regulatory element-binding protein 1 and nuclear factor kβ as compared to those of the STZ group. Apart from modulation of transcription factor expression, the expression of fatty acid synthase, long chain acyl CoA synthase, and malonyl-CoA-acyl carrier protein transacylase was lowered by flax/fish oil treatment. Serum cholesterol, triglycerides, and VLDL were also significantly reduced in the treatment groups as compared to those in the STZ group. Although pathological abnormalities were seen in the liver and kidneys of rats on metformin, no significant changes in liver/renal function markers were observed at day 15 and day 30 of the treatment groups. Flax/fish oil had protective effects toward pathological abnormalities in the liver and kidney. Flax/fish oil improved lipid profile and alkaline phosphatase at day 30 as compared to that at day 15. Conclusions The present study demonstrates potential beneficial effects of metformin and flax/fish oil intervention in improving serum lipid profile by regulating the expression of transcription factors and genes involved in lipid metabolism in diabetic rats. In addition, these interventions also lowered the expression of atherogenic cytokines. The protective effects of flax/fish oil are worth investigating in human subjects on metformin monotherapy.

Description: Scope Insulin resistance is associated with impaired cardiac function, but the underlying molecular abnormalities are largely unexplained. Bilberry anthocyanin (BAcn) may be protective, as it appears to potentiate insulin action. Methods Rats were randomly allocated to control, sucrose-fed (SF) or sucrose-fed + BAcn diets (SF-A) for 15 weeks. Cardiac insulin signalling genes and proteins were quantified using reverse transcription quantitative real-time polymerase chain reaction and western blots. Results Glucose tolerance was not different with treatment. SF showed lower ( p  〈 0.05) ferric reducing antioxidant power, which increased with BAcn. SF resulted in significantly decreased ( p  〈 0.05) expression of 10 genes: acetyl-coenzyme A carboxylase alpha; V-Akt murine thymoma viral oncogene homolog 1; Bcl2-like 1; cytosine-cytosine-adenosine-adenosine-thymidine/enhancer binding protein; FK506 binding protein 12-rapamycin associated; glycerol-3-phosphate dehydrogenase 1 (soluble); solute carrier family 2 (facilitated glucose transporter), member 1, 4; hexokinase 2; and thyroglobulin. SF-A prevented these changes. Compared to SF-A, SF up-regulated ( p  〈 0.05) complement factor D and phosphoinositide-3-kinase, regulatory subunit1 (α); sterol regulatory element binding transcription factor 1 was down-regulated ( p  〈 0.05). SF increased ( p  〈 0.05) cardiac phospholamban and decreased phosphorylated troponin I, which were not attenuated by BAcn. Compared to control or SF, SF-A resulted in significantly lower ( p  〈 0.05) 5′-AMP-activated protein kinase. Conclusions SF lowered antioxidant capacity and changed the expression of insulin signalling genes, which were modulated by BAcn.

Description: The optimal ratio of omega-6 to omega-3 polyunsaturated fatty acids (PUFAs) is important for keeping the homeostasis of biological processes and metabolism, yet the underlying biological mechanism is poorly understood. The objective of this study was to identify changes in the pig liver transcriptome induced by a diet enriched with omega-6 and omega-3 fatty acids and to characterize the biological mechanisms related to PUFA metabolism. Polish Landrace pigs ( n  = 12) were fed diet enriched with linoleic acid (LA, omega-6) and α-linolenic acid (ALA, omega-3) or standard diet as a control. The fatty acid profiling was assayed in order to verify how feeding influenced the fatty acid content in the liver, and subsequently next-generation sequencing (NGS) was used to identify differentially expressed genes (DEG) between transcriptomes between dietary groups. The biological mechanisms and pathway interaction networks were identified using DAVID and Cytoscape tools. Fatty acid profile analysis indicated a higher contribution of PUFAs in the liver for LA- and ALA-enriched diet group, particularly for the omega-3 fatty acid family, but not omega-6. Next-generation sequencing identified 3565 DEG, 1484 of which were induced and 2081 were suppressed by PUFA supplementation. A low ratio of omega-6/omega-3 fatty acids resulted in the modulation of fatty acid metabolism pathways and over-representation of genes involved in energy metabolism, signal transduction, and immune response pathways. In conclusion, a diet enriched with omega-6 and omega-3 fatty acids altered the transcriptomic profile of the pig liver and would influence animal health status.

Description: Background Caloric restriction (CR) is considered to increase lifespan and to prevent various age-related diseases in different nonhuman organisms. Only a limited number of CR studies have been performed on humans, and results put CR as a beneficial tool to decrease risk factors in several age-related diseases. The question remains at what age CR should be implemented to be most effective with respect to healthy aging. The aim of our study was to elucidate the role of age in the transcriptional response to a completely controlled 30 % CR diet on immune cells, as immune response is affected during aging. Ten healthy young men, aged 20–28, and nine healthy old men, aged 64–85, were subjected to a 2-week weight maintenance diet, followed by 3 weeks of 30 % CR. Before and after 30 % CR, the whole genome gene expression in peripheral blood mononuclear cells (PBMCs) was assessed. Results Expression of 554 genes showed a different response between young and old men upon CR. Gene set enrichment analysis revealed a downregulation of gene sets involved in the immune response in young but not in old men. At baseline, immune response-related genes were higher expressed in old compared to young men. Upstream regulator analyses revealed that most potential regulators were controlling the immune response. Conclusions Based on the gene expression data, we theorise that a short period of CR is not effective in old men regarding immune-related pathways while it is effective in young men. Trial registration ClinicalTrials.gov, NCT00561145

Description: Background Environmental factors are well-known causes of diseases. However, aside from a handful of risk indicators, genes’ encoding susceptibility to chronic illnesses and their associated environmental triggers are largely unknown. In this era of increasingly rich diets, such genetic predispositions would be immensely helpful from a public health perspective. The novel transgenic mouse model with liver-specific NG37 overexpression characterized in this article identifies the diet-dependent function of NG37 in the pathogenesis of fatty liver disease and cardiac arrhythmia. Results The liver-specific NG37 overexpression transgenic mouse model described here was generated using the Alb-SV40 polyA expression plasmid backbone. NG37 cDNA under control of the albumin promoter for liver-specific expression was fused with a 5′ terminal M2 FLAG sequence and a SV40 early region transcription terminator/polyadenylation site attached at the 3′-UTR. These NG37 transgenic mice developed normally and were physiologically normal on a standard diet. However, in comparison to non-transgenic (nTG) litter mates, these mice develop dramatic phenotypes within 12–18 days of starting a high-fat diet: (i) increased body weight (28.5 ± 12.3 g), (ii) increased liver weight (87.4 ± 35.7 mg), (iii) increased heart weight (140 ± 38.4 mg), and (iv) cardiac arrhythmia. The enlarged livers of high-fat diet NG37 transgenic mice was histologically similar to human fatty liver disease and contained Maltese cross birefringent active depositions in hepatocytes that are indicative of fatty liver disease. We also confirmed via X-ray diffraction the steatotic vesicles in the diseased hepatocytes of our high-fat diet NG37 mice was composed of cholesteryl derivatives also found in human fatty liver disease. In addition to cardiac enlargement, NG37 transgenic mice on high-fat diet also exhibited highly irregular bradycardia not present in either high-fat diet nTG littermates or normal-diet transgenic litter mates. Conclusions The dramatic high-fat diet-dependent symptoms (increased body weight, cardiac enlargement, fatty liver, and cardiac arrhythmias) characterized in our liver-specific NG37 overexpression mouse model identifies NG37 as a gene encoding latent lipid metabolism pathology induced only in the presence of an environmental factor relevant to human health: high-fat diet.

Description: Biomarkers of nutrient intake or nutrient status are important objective measures of foods/nutrients as one of the most important environmental factors people are exposed to. It is very difficult to obtain accurate data on individual food intake, and there is a large variation of nutrient composition of foods consumed in a population. Thus, it is difficult to obtain precise measures of exposure to different nutrients and thereby be able to understand the relationship between diet, health, and disease. This is the background for investing considerable resources in studying biomarkers of nutrients believed to be important in our foods. Modern technology with high sensitivity and specificity concerning many nutrient biomarkers has allowed an interesting development with analyses of very small amounts of blood or tissue material. In combination with non-professional collection of blood by finger-pricking and collection on filters or sticks, this may make collection of samples and analyses of biomarkers much more available for scientists as well as health professionals and even lay people in particular in relation to the marked trend of self-monitoring of body functions linked to mobile phone technology. Assuming standard operating procedures are used for collection, drying, transport, extraction, and analysis of samples, it turns out that many analytes of nutritional interest can be measured like metabolites, drugs, lipids, vitamins, minerals, and many types of peptides and proteins. The advantage of this alternative sampling technology is that non-professionals can collect, dry, and mail the samples; the samples can often be stored under room temperature in a dry atmosphere, requiring small amounts of blood. Another promising area is the potential relation between the microbiome and biomarkers that may be measured in feces as well as in blood.

Description: Background The Nile rat (NR, Arvicanthis niloticus ) is a model of carbohydrate-induced type 2 diabetes mellitus (T2DM) and the metabolic syndrome. A previous study found that palm fruit juice (PFJ) delayed or prevented diabetes and in some cases even reversed its early stages in young NRs. However, the molecular mechanisms by which PFJ exerts these anti-diabetic effects are unknown. In this study, the transcriptomic effects of PFJ were studied in young male NRs, using microarray gene expression analysis. Methods Three-week-old weanling NRs were fed either a high-carbohydrate diet (%En from carbohydrate/fat/protein = 70:10:20, 16.7 kJ/g; n  = 8) or the same high-carbohydrate diet supplemented with PFJ (415 ml of 13,000-ppm gallic acid equivalent (GAE) for a final concentration of 5.4 g GAE per kg diet or 2.7 g per 2000 kcal; n  = 8). Livers were obtained from these NRs for microarray gene expression analysis using Illumina MouseRef-8 Version 2 Expression BeadChips. Microarray data were analysed along with the physiological parameters of diabetes. Results Compared to the control group, 71 genes were up-regulated while 108 were down-regulated in the group supplemented with PFJ. Among hepatic genes up-regulated were apolipoproteins related to high-density lipoproteins (HDL) and genes involved in hepatic detoxification, while those down-regulated were related to insulin signalling and fibrosis. Conclusion The results obtained suggest that the anti-diabetic effects of PFJ may be due to mechanisms other than an increase in insulin secretion.

Description: Background Fetal exposure to a maternal low protein diet during rat pregnancy is associated with hypertension, renal dysfunction and metabolic disturbance in adult life. These effects are present when dietary manipulations target only the first half of pregnancy. It was hypothesised that early gestation protein restriction would impact upon placental gene expression and that this may give clues to the mechanism which links maternal diet to later consequences. Methods Pregnant rats were fed control or a low protein diet from conception to day 13 gestation. Placentas were collected and RNA sequencing performed using the Illumina platform. Results Protein restriction down-regulated 67 genes and up-regulated 24 genes in the placenta. Ingenuity pathway analysis showed significant enrichment in pathways related to cholesterol and lipoprotein transport and metabolism, including atherosclerosis signalling, clathrin-mediated endocytosis, LXR/RXR and FXR/RXR activation. Genes at the centre of these processes included the apolipoproteins ApoB, ApoA2 and ApoC2, microsomal triglyceride transfer protein (Mttp), the clathrin-endocytosis receptor cubilin, the transcription factor retinol binding protein 4 (Rbp4) and transerythrin (Ttr; a retinol and thyroid hormone transporter). Real-time PCR measurements largely confirmed the findings of RNASeq and indicated that the impact of protein restriction was often striking (cubilin up-regulated 32-fold, apoC2 up-regulated 17.6-fold). The findings show that gene expression in specific pathways is modulated by maternal protein restriction in the day-13 rat placenta. Conclusions Changes in cholesterol transport may contribute to altered tissue development in the fetus and hence programme risk of disease in later life.

Description: Background We have previously reported that γ- and δ-tocotrienols (γ- and δ-T3) induce gene expression and apoptosis in human breast cancer cells (MDA-MB-231 and MCF-7). This effect is mediated, at least in part, by a specific binding and activation of the estrogen receptor-β (ERβ). Transcriptomic data obtained within our previous studies, interrogated by different bioinformatic tools, suggested the existence of an alternative pathway, activated by specific T3 forms and leading to apoptosis, also in tumor cells not expressing ER. In order to confirm this hypothesis, we conducted a study in HeLa cells, a line of human cervical cancer cells void of any canonical ER form. Results Cells were synchronized by starvation and treated either with a T3-rich fraction from palm oil (10–20 μg/ml) or with purified α-, γ-, and δ-T3 (5–20 μg/ml). α-tocopherol (TOC) was utilized as a negative control. Apoptosis, accompanied by a significant expression of caspase 8, caspase 10, and caspase 12 was observed at 12 h from treatments. The interrogation of data obtained from transcriptomic platforms (NuGO Affymetrix Human Genechip NuGO_Hs1a520180), further confirmed by RT-PCR, suggested that the administration of γ- and δ-T3 associates with Ca 2+ release. Data interrogation were confirmed in living cells; in fact, Ca-dependent signals were observed followed by the expression and activation of IRE-1α and of other molecules involved in the unfolded protein response, the core pathway coping with endoplasmic reticulum stress in eukaryotic cells, finally leading to apoptosis. Conclusions Our study demonstrates that γ- and δ-T3 induce apoptosis also in tumor cells lacking of ERβ by triggering signals originating from endoplasmic reticulum stress. Our observations suggest that tocotrienols could have a significant role in tumor cell physiology and a possible therapeutic potential.

Description: Background The kidney is a major organ in which fluid balance and waste excretion is regulated. For the kidney to achieve maturity with functions, normal renal developmental processes need to occur. Comprehensive genetic programs underlying renal development during the prenatal period have been widely studied. However, postnatal renal development, from infancy to the juvenile period, has not been studied yet. Here, we investigated whether structural and functional kidney development was still ongoing in early life by analyzing the renal transcriptional networks of infant (4 weeks old) and juvenile (7 weeks old) mice. We further examined the effects of dehydration on kidney development to unravel the mechanistic bases underlying deteriorative impact of pediatric dehydration on renal development. Methods 3-week-old infant mice that just finished weaning period were provided limited access to a water for fifteen minutes per day for one week (RES 1W) and four weeks (RES 4W) to induce dehydration while control group consumed water ad libitum with free access to the water bottle. Transcriptome analysis was conducted to understand physiological changes during postnatal renal development and dehydration. Results Kidneys in 4-week- and 7-week-old mice showed significantly distinctive functional gene networks. Gene sets related to cell cycle regulators, fetal kidney patterning molecules, and immature basement membrane integrity were upregulated in infantile kidneys while heightened expressions of genes associated with ion transport and drug metabolism were observed in juvenile kidneys. Dehydration during infancy suppressed renal growth by interrupting the SHH signaling pathway, which targets cell cycle regulators. Importantly, it is likely that disruption of the developmental program ultimately led to a decline in gene expression associated with basement membrane integrity. Conclusions Altogether, we demonstrate transcriptional events during renal development in infancy and show that the impacts of inadequate water intake in the early postnatal state heavily rely on the impairment of normal renal development. Here, we provide a meaningful perspective of renal development in infancy with a molecular and physiological explanation of why infants are more vulnerable to dehydration than adults. These results provide new insights into the molecular effects of dehydration on renal physiology and indicate that optimal nutritional interventions are necessary for pediatric renal development.