Omega-3 rich diets have been shown to improve inflammatory status. However, in an ex vivo system of human blood cells, the efficacy of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) modulating lipid metabolism and cytokine response is attenuated in overweight subjects and shows high inter-individual variability. This suggests that obesity may be exerting a synergistic effect with genetic background disturbing the anti-inflammatory potential of omega-3 long-chain polyunsaturated fatty acids (PUFA). In the present work, a genetic score aiming to explore the risk associated to low grade inflammation and obesity (LGI-Ob) has been elaborated and assessed as a tool to contribute to discern population at risk for metabolic syndrome. Pro-inflammatory gene expression and cytokine production as a response to omega-3 were associated with LGI-Ob score; and lower anti-inflammatory effect of PUFA was observed in subjects with a high genetic score. Furthermore, overweight/obese individuals showed positive correlation of both plasma C-Reactive Protein and triglyceride/HDLc-index with LGI-Ob; and high LGI-Ob score was associated with greater hypertension (p = 0.047), Type 2 diabetes (p = 0.026), and metabolic risk (p = 0.021). The study shows that genetic variation can influence inflammation and omega-3 response, and that the LGI-Ob score could be a useful tool to classify subjects at inflammatory risk and more prone to suffer metabolic syndrome and associated metabolic disturbances. Full article

Although, for decades, increased serum bilirubin concentrations were considered a threatening sign of underlying liver disease and had been associated with neonatal jaundice, data from recent years show that bilirubin is a powerful antioxidant and suggest that slightly increased serum bilirubin concentrations are protective against oxidative stress-related diseases, such as cardiovascular diseases. Therefore, a better understanding of the gene-diet interactions in determining serum bilirubin concentrations is needed. None of the previous genome-wide association studies (GWAS) on bilirubin concentrations has been stratified by sex. Therefore, considering the increasing interest in incorporating the gender perspective into nutritional genomics, our main aim was to carry out a GWAS on total serum bilirubin concentrations in a Mediterranean population with metabolic syndrome, stratified by sex. Our secondary aim was to explore, as a pilot study, the presence of gene-diet interactions at the GWAS level. We included 430 participants (188 men and 242 women, aged 55–75 years, and with metabolic syndrome) in the PREDIMED Plus-Valencia study. Global and sex-specific GWAS were undertaken to analyze associations and gene-diet interaction on total serum bilirubin. Adherence (low and high) to the Mediterranean diet (MedDiet) was analyzed as the dietary modulator. In the GWAS, we detected more than 55 SNPs associated with serum bilirubin at p < 5 × 10⁻⁸ (GWAS level). The top-ranked were four SNPs (rs4148325 (p = 9.25 × 10⁻²⁴), rs4148324 (p = 9.48 × 10⁻²⁴), rs6742078 (p = 1.29 × 10⁻²³), rs887829 (p = 1.39 × 10⁻²³), and the rs4148324 (p = 9.48 × 10⁻²⁴)) in the UGT1A1 (UDP glucuronosyltransferase family 1 member A1) gene, which replicated previous findings revealing the UGT1A1 as the major locus. In the sex-specific GWAS, the top-ranked SNPs at the GWAS level were similar in men and women (the lead SNP was the rs4148324-UGT1A1 in both men (p = 4.77 × 10⁻¹¹) and women (p = 2.15 × 10⁻¹⁴), which shows homogeneous genetic results for the major locus. There was more sex-specific heterogeneity for other minor genes associated at the suggestive level of GWAS significance (p < 1 × 10⁻⁵). We did not detect any gene-MedDiet interaction at p < 1 × 10⁻⁵ for the major genetic locus, but we detected some gene-MedDiet interactions with other genes at p < 1 × 10⁻⁵, and even at the GWAS level for the IL17B gene (p = 3.14 × 10⁻⁸). These interaction results, however, should be interpreted with caution due to our small sample size. In conclusion, our study provides new data, with a gender perspective, on genes associated with total serum bilirubin concentrations in men and women, and suggests possible additional modulations by adherence to MedDiet. Full article

This study investigated whether the association between postprandial plasma glucose (PPG) is affected by five type 2 diabetes mellitus (T2DM) susceptibility genes, and whether four weeks of yogurt consumption would affect these responses. We performed a single-arm intervention study in young nondiabetic Japanese participants, who consumed 150 g yogurt daily for four weeks, after which a rice test meal containing 50 g carbohydrate was administered. PPG and postprandial serum insulin (PSI) were measured between 0 and 120 mins at baseline and after the intervention. Genetic risk was evaluated by weighted genetic risk score (GRS) according to published methodology, and participants were assigned to one of two groups (n = 17: L-GRS group and n = 15: H-GRS group) according to the median of weighted GRS. At baseline, the H-GRS group had higher glucose area under the curve_{0–120 min} after intake of the test meal than the L-GRS group (2175 ± 248 mg/dL.min vs. 1348 ± 199 mg/dL.min, p < 0.001), but there were no significant differences after the yogurt intervention. However, there was an improvement in PSI in the H-GRS group compared with baseline. These results suggest that habitual yogurt consumption may improve glucose and insulin responses in nondiabetic subjects who have genetically higher PPG. Full article

There is growing interest in relating taste perception to diet and healthy aging. However, there is still limited information on the influence of age, sex and genetics on taste acuity as well as on the relationship between taste perception and taste preferences. We have analysed the influence of age on the intensity rating of the five basic tastes: sweet, salty, bitter, sour and umami (separately and jointly in a “total taste score”) and their modulation by sex and genetics in a relatively healthy population (men and women) aged 18–80 years (n = 1020 Caucasian European participants). Taste perception was determined by challenging subjects with solutions of the five basic tastes using standard prototypical tastants (6-n-propylthiouracil (PROP), NaCl, sucrose, monopotassium glutamate and citric acid) at 5 increasing concentrations (I to V). We also measured taste preferences and determined the polymorphisms of the genes taste 2 receptor member 38 (TAS2R38), taste 1 receptor member 2 (TAS2R38) and sodium channel epithelial 1 beta subunit (SCNN1B), as TAS2R38-rs713598, TAS1R2-rs35874116 and SCNN1B-rs239345 respectively. We found a statistically significant decrease in taste perception (“total taste score”) with increasing age for all the concentrations analysed. This association was stronger for the higher concentrations (p = 0.028; p = 0.012; p = 0.005; p = 4.20 × 10⁻⁵ and p = 1.48 × 10⁻⁷, for I to V in the multivariable-adjusted models). When we analysed taste qualities (using concentration V), the intensity rating of all the 5 tastes was diminished with age (p < 0.05 for all). This inverse association differed depending on the test quality, being higher for bitter (PROP) and sour. Women perceived taste significantly more intense than men (p = 1.4 × 10⁻⁸ for total taste score). However, there were differences depending on the taste, umami being the lowest (p = 0.069). There was a complex association between the ability to perceive a taste and the preference for the same. Significant associations were, nevertheless, found between a higher perception of sour taste and a higher preference for it in women. In contrast, the higher perception of sweet was significantly associated with a higher preference for bitter in both, men and women. The TAS2R38-rs713598 was strongly associated with bitter (PROP) taste (p = 1.38 × 10⁻⁵⁰), having a significant interaction with sex (p = 0.030). The TAS1R2-rs35874116 was not significantly associated with sweet, whereas the SCNN1B-rs239345 was associated (p = 0.040) with salty taste. In conclusion, the inverse association between age and perceived taste intensity as well as the additional influence of sex and some genetic polymorphisms give rise to large inter-individual differences in taste perception and taste preferences that should be taken into account in future studies and for applications in precision nutrition for healthy aging. Full article

Precision nutrition aims to make dietary recommendations of a more personalized nature possible, to optimize the prevention or delay of a disease and to improve health. Therefore, the characteristics (including sex) of an individual have to be taken into account as well as a series of omics markers. The results of nutritional genomics studies are crucial to generate the evidence needed so that precision nutrition can be applied. Although sex is one of the fundamental variables for making recommendations, at present, the nutritional genomics studies undertaken have not analyzed, systematically and with a gender perspective, the heterogeneity/homogeneity in gene-diet interactions on the different phenotypes studied, thus there is little information available on this issue and needs to be improved. Here we argue for the need to incorporate the gender perspective in nutritional genomics studies, present the general context, analyze the differences between sex and gender, as well as the limitations to measuring them and to detecting specific sex-gene or sex-phenotype associations, both at the specific gene level or in genome-wide-association studies. We analyzed the main sex-specific gene-diet interactions published to date and their main limitations and present guidelines with recommendations to be followed when undertaking new nutritional genomics studies incorporating the gender perspective. Full article

Vitamin E (VE) has a recognized leading role as a contributor to the protection of cell constituents from oxidative damage. However, evidence suggests that the health benefits of VE go far beyond that of an antioxidant acting in lipophilic environments. In humans, VE is channeled toward pathways dealing with lipoproteins and cholesterol, underlining its relevance in lipid handling and metabolism. In this context, both VE intake and status may be relevant in physiopathological conditions associated with disturbances in lipid metabolism or concomitant with oxidative stress, such as obesity. However, dietary reference values for VE in obese populations have not yet been defined, and VE supplementation trials show contradictory results. Therefore, a better understanding of the role of genetic variants in genes involved in VE metabolism may be crucial to exert dietary recommendations with a higher degree of precision. In particular, genetic variability should be taken into account in targets concerning VE bioavailability per se or concomitant with impaired lipoprotein transport. Genetic variants associated with impaired VE liver balance, and the handling/resolution of oxidative stress might also be relevant, but the core information that exists at present is insufficient to deliver precise recommendations. Full article

Protein encoding genes constitute a small fraction of mammalian genomes. In addition to the protein coding genes, there are other functional units within the genome that are transcribed, but not translated into protein, the so called non-coding RNAs. There are many types of non-coding RNAs that have been identified and shown to have important roles in regulating gene expression either at the transcriptional or post-transcriptional level. A number of recent studies have highlighted that dietary manipulation in mammals can influence the expression or function of a number of classes of non-coding RNAs that contribute to the protein translation machinery. The identification of protein translation as a common target for nutritional regulation underscores the need to investigate how this may mechanistically contribute to phenotypes and diseases that are modified by nutritional intervention. Finally, we describe the state of the art and the application of emerging ‘-omics’ technologies to address the regulation of protein translation in response to diet. Full article

The search for genetic risk factors in type-II diabetes has been hindered by a failure to consider dietary variables. Dietary nutrients impact metabolic disease risk and severity and are essential to maintaining metabolic health. Genetic variation between individuals confers differences in metabolism, which directly impacts response to diet. Most studies attempting to identify genetic risk factors in disease fail to incorporate dietary components, and thus are ill-equipped to capture the breadth of the genome’s impact on metabolism. Understanding how genetic background interacts with nutrients holds the key to predicting and preventing metabolic diseases through the implementation of personalized nutrition. Dysregulation of iron homeostasis is associated with type-II diabetes, but the link between dietary iron and metabolic dysfunction is poorly defined. High iron burden in adipose tissue induces insulin resistance, but the mechanisms underlying adipose iron accumulation remain unknown. Hepcidin controls dietary iron absorption and distribution in metabolic tissues, but it is unknown whether genetic variation influencing hepcidin expression modifies susceptibility to dietary iron-induced insulin resistance. This review highlights discoveries concerning the axis of iron homeostasis and adipose function and suggests that genetic variation underlying dietary iron metabolism is an understudied component of metabolic disease. Full article

Soy consumption has been associated with many potential health benefits in reducing chronic diseases such as obesity, cardiovascular disease, insulin-resistance/type II diabetes, certain type of cancers, and immune disorders. These physiological functions have been attributed to soy proteins either as intact soy protein or more commonly as functional or bioactive peptides derived from soybean processing. These findings have led to the approval of a health claim in the USA regarding the ability of soy proteins in reducing the risk for coronary heart disease and the acceptance of a health claim in Canada that soy protein can help lower cholesterol levels. Using different approaches, many soy bioactive peptides that have a variety of physiological functions such as hypolipidemic, anti-hypertensive, and anti-cancer properties, and anti-inflammatory, antioxidant, and immunomodulatory effects have been identified. Some soy peptides like lunasin and soymorphins possess more than one of these properties and play a role in the prevention of multiple chronic diseases. Overall, progress has been made in understanding the functional and bioactive components of soy. However, more studies are required to further identify their target organs, and elucidate their biological mechanisms of action in order to be potentially used as functional foods or even therapeutics for the prevention or treatment of chronic diseases. Full article

Approximately 5.7 million U.S. adults have been diagnosed with heart failure (HF). More concerning is that one in nine U.S. deaths included HF as a contributing cause. Current HF drugs (e.g., β-blockers, ACEi) target intracellular signaling cascades downstream of cell surface receptors to prevent cardiac pump dysfunction. However, these drugs fail to target other redundant intracellular signaling pathways and, therefore, limit drug efficacy. As such, it has been postulated that compounds designed to target shared downstream mediators of these signaling pathways would be more efficacious for the treatment of HF. Histone deacetylation has been linked as a key pathogenetic element for the development of HF. Lysine residues undergo diverse and reversible post-translational modifications that include acetylation and have historically been studied as epigenetic modifiers of histone tails within chromatin that provide an important mechanism for regulating gene expression. Of recent, bioactive compounds within our diet have been linked to the regulation of gene expression, in part, through regulation of the epi-genome. It has been reported that food bioactives regulate histone acetylation via direct regulation of writer (histone acetyl transferases, HATs) and eraser (histone deacetylases, HDACs) proteins. Therefore, bioactive food compounds offer unique therapeutic strategies as epigenetic modifiers of heart failure. This review will highlight food bio-actives as modifiers of histone deacetylase activity in the heart. Full article