Introduction: Genes encoding catechol-O-methyl-transferase (COMT) and adenosine A2A receptor (ADORA2A) have been shown to influence cognitive performances and responses to caffeine intake during prolonged wakefulness. The rs4680 single-nucleotide polymorphism (SNP) of COMT differentiates on memory score and circulating levels of the neurotrophic factor IGF-1. This study aimed to determine the kinetics of IGF-1, testosterone, and cortisol concentrations during prolonged wakefulness under caffeine or placebo intake in 37 healthy participants, and to analyze whether the responses are dependent on COMT rs4680 or ADORA2A rs5751876 SNPs.
Methods: In caffeine (2.5 mg/kg, twice over 24 h) or placebo-controlled condition, blood sampling was performed at 1 h (08:00, baseline), 11 h, 13 h, 25 h (08:00 next day), 35 h, and 37 h of prolonged wakefulness, and at 08:00 after one night of recovery sleep, to assess hormonal concentrations. Genotyping was performed on blood cells.
Results: Results indicated a significant increase in IGF-1 levels after 25, 35, and 37 h of prolonged wakefulness in the placebo condition, in subjects carrying the homozygous COMT A/A genotype only (expressed in absolute values [±SEM]: 118 ± 8, 121 ± 10, and 121 ± 10 vs. 105 ± 7 ng/mL for A/A, 127 ± 11, 128 ± 12, and 129 ± 13 vs. 120 ± 11 ng/mL for G/G, and 106 ± 9, 110 ± 10, and 106 ± 10 vs. 101 ± 8 ng/mL for G/A, after 25, 35, and 37 h of wakefulness versus 1 h; p < 0.05, condition X time X SNP). Acute caffeine intake exerted a COMT genotype-dependent reducing effect on IGF-1 kinetic response (104 ± 26, 107 ± 27, and 106 ± 26 vs. 100 ± 25 ng/mL for A/A genotype, at 25, 35, and 37 h of wakefulness vs. 1 h; p < 0.05 condition X time X SNP), plus on resting levels after overnight recovery (102 ± 5 vs. 113 ± 6 ng/mL) (p < 0.05, condition X SNP). Testosterone and cortisol concentrations decreased during wakefulness, and caffeine alleviated the testosterone reduction, unrelated to the COMT polymorphism. No significant main effect of the ADORA2A SNP was shown regardless of hormonal responses.
Conclusion: Our results indicated that the COMT polymorphism interaction is important in determining the IGF-1 neurotrophic response to sleep deprivation with caffeine intake (NCT03859882).
Introduction: Rate-limiting enzymes (RLEs) are innate slow points in metabolic pathways, and many function in bio-processes related to nutrient sensing. Many RLEs carry causal mutations relevant to inherited metabolic disorders. Because the activity of RLEs in cardiovascular health is poorly characterized, our objective was to assess their involvement in cardiometabolic health and disease and where altered biophysical and biochemical functions can promote disease.
Methods: A dataset of 380 human RLEs was compared to protein and gene datasets for factors likely to contribute to cardiometabolic disease, including proteins showing significant age-related altered expression in blood and genetic loci with variants that associate with common cardiometabolic phenotypes. The biochemical reactions catalyzed by RLEs were evaluated for metabolites enriched in RLE subsets associating with various cardiometabolic phenotypes. Most significance tests were based on Z-score enrichment converted to p values with a normal distribution function.
Results: Of 380 RLEs analyzed, 112 function in mitochondria, and 53 are assigned to inherited metabolic disorders. There was a depletion of RLE proteins known as aging biomarkers. At the gene level, RLEs were assessed for common genetic variants that associated with important cardiometabolic traits of LDL-cholesterol or any of the five outcomes pertinent to metabolic syndrome. This revealed several RLEs with links to cardiometabolic traits, from a minimum of 26 for HDL-cholesterol to a maximum of 45 for plasma glucose. Analysis of these GWAS-linked RLEs for enrichment of the molecular constituents of the catalyzed reactions disclosed a number of significant phenotype-metabolite links. These included blood pressure with acetate (p = 2.2 × 10-4) and NADP+ (p = 0.0091), plasma HDL-cholesterol and triglyceride with diacylglycerol (p = 2.6 × 10-5, 6.4 × 10-5, respectively) and diolein (p = 2.2 × 10-6, 5.9 × 10-6), and waist circumference with
Conclusion: In the context of cardiometabolic health, aging, and disease, these results highlight key diet-derived metabolites that are central to specific rate-limited processes that are linked to cardiometabolic health. These metabolites include acetate and diacylglycerol, pertinent to blood pressure and triglycerides, respectively, as well as diacylglycerol and HDL-cholesterol.
Background: Our daily intake of food provides nutrients for the maintenance of health, growth, and development. The field of nutrigenomics aims to link dietary intake/nutrients to changes in epigenetic status and gene expression.
Summary: Although the relationship between our diet and our genes in under intense investigation, there is still a significant aspect of our genome that has received little attention with regard to this. In the past 15 years, the importance of genome organization has become increasingly evident, with research identifying small-scale local changes to large segments of the genome dynamically repositioning within the nucleus in response to/or mediating change in gene expression. The discovery of these dynamic processes and organization maybe as significant as dynamic plate tectonics is to geology, there is little information tying genome organization to specific nutrients or dietary intake.
Key messages: Here, we detail key principles of genome organization and structure, with emphasis on genome folding and organization, and link how these contribute to our future understand of nutrigenomics.
Introduction: Exposure to discrimination has emerged as a risk factor for obesity. It remains unclear, however, whether the genotype of the individual can modulate the sensitivity or response to discrimination exposure (gene × environment interaction) or increase the likelihood of experiencing discrimination (gene-environment correlation).
Methods: This was an observational study of 4,102 white/European Americans in the Health and Retirement Study with self-reported, biological assessments, and genotyped data from 2006 to 2014. Discrimination was operationalized using the average of nine Everyday Discrimination Scale items. Polygenic risk scores (PRSs) for body mass index (BMI) and waist circumference (WC) were calculated using the weighted sum of risk alleles based on studies conducted by the Genetic Investigation of Anthropometric Traits (GIANT) consortium.
Results: We found that greater PRS-BMI was significantly associated with more reports of discrimination (β = 0.04 ± 0.02; p = 0.037). Further analysis showed that measured BMI partially mediated the association between PRS-BMI and discrimination. There was no evidence that the association between discrimination and BMI, or the association between discrimination and WC, differed by PRS-BMI or PRS-WC, respectively.
Conclusion: Our findings suggest that individuals with genetic liability for obesity may experience greater discrimination in their lifetime, consistent with a gene-environment correlation hypothesis. There was no evidence of a gene-environment interaction. More genome-wide association studies in diverse populations are needed to improve generalizability of study findings. In the meantime, prevention and clinical intervention efforts that seek to reduce exposure to all forms of discrimination may help reduce obesity at the population level.
Introduction: Although investigations into the emerging field of nutrigenomics are relatively limited and more research in this field is required, experts agree that there is potential for it to be incorporated into health care practice. If health care professionals can promote healthy dietary behavior based on nutrigenomic testing, it can assist in addressing the health consequences of poor diet and lightning the strain on the South African health care system.
Methods: Registered dietitians (RDs) and general practitioners (GPs) registered with the Health Professions Council of South Africa (HPCSA) who obtained their qualification in South Africa (SA) were eligible to participate in this cross-sectional study. Participants were identified using convenience and snowball sampling. A self-administered electronic survey using EvaSys Software® was completed by those that agreed to participate.
Results: Nearly all RDs (97.3%), but less than a third of GPs (30.4%), had heard of the term nutrigenomics. Approximately three-quarters of RDs (74.7%) and GPs (73.9%) had or would personally consider undergoing genetic testing. More than 40% (43.5%) of RDs ranked direct-to-consumer genetic testing companies as the most equipped, while 31.8% of GPs ranked RDs as the most equipped to provide patients with nutrigenomic services. Both RDs and GPs ranked similar reasons as "strongly agree" for why consumers were motivated to make use of nutrigenomic services, which included "motivated by a desire to prevent or manage disease" (56.7%), "prevent a disease based on family history" (65.9%), "control health outcomes based on family history" (54.9%), and "improve overall health-related quality of life" (48.6%). Cost concerns were reported as the greatest barrier to implementing nutrigenomic services (75.7%). Other barriers included confidentiality issues (47.8%) and moral concerns (37.3%). Greater individualization of diet prescription (66.5%), stronger foundations for nutrition recommendations (62.4%), and dietary prescriptions that would manage or prevent certain diseases more effectively (59.0%) were all perceived as benefits of including nutrigenomics in practice.
Conclusion: This study identified perceived consumer motivators and barriers that might affect the willingness to seek nutrigenomic services in SA. In addition, the need for more nutrigenomic training opportunities, including the planning of personalized diets based on genetic testing results and interpretation of results, was confirmed. However, both RDs and GPs felt that the emerging field of nutrigenomics needs further development before it can be applied effectively in routine private and public health care in SA.
Introduction: Single-nucleotide polymorphism (SNP) rs9939609 in the FTO gene has been associated with dietary intake and appetite traits, mainly in participants with obesity; however, it remains widely unexplored in normal weight participants. Thus, the aims of this study were (1) to compare the changes in subjective appetite sensations, ghrelin, and insulin concentrations according to the SNP rs9939609 T>A in FTO and (2) to compare dietary intake between rs9939609 genotype groups in normal weight young participants.
Methods: We conducted a quasi-experimental study involving 88 normal weight participants to analyze subjective perception of appetite, hormonal response for hunger and satiety, and dietary intake according to the rs9939609 SNP. Participants received a standardized single breakfast. Visual analogue scales (VAS) were utilized for assessing the subjective perception of appetite at fasting and immediately after breakfast and at 30, 60, 90, and 120 min postprandially. Glucose, lipid profile, ghrelin, and insulin were measured at fasting and at 120 min after breakfast. Dietary intake was assessed with a 3-day food record. The SNP was determined by allelic discrimination with TaqMan probes. To compare dietetic, biochemical, and the subjective appetite sensations, Student t test, ANCOVA test, and the repeated measures ANOVA were used. The linear regression model and the linear mixed model were used for the association analysis. Pearson correlation was used to test the correlation between two quantitative variables.
Results: A total of 88 people participated, 81.8% were female, with a mean body mass index of 21.8 ± 2.0 kg/m2 and a mean age of 20.6 ± 2.0. Genotype frequencies of the rs9939609 SNP were 52% for the TT allele and 48% for the TA/AA. The subjective perception of appetite named hunger, fullness, satiety, desire to eat, and prospective food consumption were similar between genotypes of the rs9939609. Participants with the TA/AA genotype showed a higher intake of added sugar (p = 0.039) than TT participants. No differences were found in ghrelin, insulin, glucose, or lipid parameters between genotypes.
Conclusion: Carriers of the A allele from FTO gene SNP rs9939609 may have an increased preference for foods, specifically for added sugars.
Introduction: Despite the prevalence of depression and anxiety worldwide, their aetiologies remain unclear, and they can be difficult to diagnose and treat. Changes in salt-taste perception have been found in both conditions. Single-nucleotide polymorphisms (SNPs) in the salt-taste-related gene, TRPV1, have been associated with alterations to salt-taste perception, preference, and sodium consumption. Diet quality is a known modifier of depression and anxiety and recently, sodium intake has been studied in mental health. However, the relationships between salt-taste genetics, depression, anxiety, and these dietary factors are yet to be elucidated.
Methods: Data from the well-characterized cross-sectional Retirement Health and Lifestyle Study (n = 536, ≥65 y) were used to explore the relationships between the salt-taste SNP TRPV1-rs8065080, levels of depression and anxiety (Hospital Anxiety and Depression Scale, HADS), estimated sodium intake, and diet quality in this secondary analysis. Standard least-squares regression and nominal logistic regression modelling were used to compare continuous and categorical variables, respectively, with analyses stratified by sex.
Results: Presence of the TRPV1-rs8065080 variant allele (C) was found to increase the likelihood of having depression (HADS) in the total population and in males. The associations remained significant after adjusting for sodium intake, three diet quality indices, and demographic variables, suggesting that TRPV1-rs8065080 genotype is driving the association with depression.
Discussion/conclusion: Future studies should explore extra-oral functions of the SNP and salt-taste receptors in the brain and the roles of neurotransmitters common to both depression and salt taste to improve the management of this increasingly prevalent and difficult-to-treat condition.
Background: The early life period marks a critical time during which the health trajectory of offspring can be shaped by external influences including maternal nutrition. Folate and choline are water-soluble micronutrients important for fetal development and involved in one-carbon metabolism. Intakes above and below the recommendations commonly occur for both of these nutrients including over-consumption of synthetic folic acid due to widespread vitamin supplement uses and discretionary fortification practices, whereas choline is under-consumed by a majority of the populations including pregnant women. Despite these intake patterns, their long-term impact on offspring health is largely unknown. Moreover, limited attention has been on the combined effects of folate and choline despite being metabolically interrelated as methyl nutrients. This review summarizes evidence from animal models and human studies investigating the role of inadequate or supplemental maternal intakes of folic acid, choline and combined effects of folic acid, and choline as modulators of health and disease in offspring. With the recent rise in the prevalence of obesity and metabolic diseases, our primary measures of interest were metabolic outcomes.
Summary: Studies examining the role of maternal intakes of folic acid and/or choline in metabolic phenotypes of offspring have mostly been conducted in animal models with a limited number of reports that consider folate and choline together. An interdependent relationship has been demonstrated between folate and choline in studies where a deficiency in one leads to metabolic aberrations in another. Both deficient and excess maternal intakes of folic acid (in varying doses) have been shown to increase risk of obesity and characteristics of the metabolic syndrome in offspring but these findings were restricted to animal studies. Potential metabolic benefits of choline have been suggested in the presence of obesogenic environment but human data were sparse. An imbalanced intake of high folic acid and inadequate choline in the gestational diet created adverse consequences consistent with the obesogenic phenotypes whereas narrowing this imbalance with high choline blocked these effects. Mechanisms by which maternal folate and/or choline influence offspring outcomes may involve epigenetic modification of gene expression with DNA methylation that can be altered globally and gene-specifically. However, the effects of epigenetic programming were inconsistent as compensatory changes in metabolic products may occur and other contributors including the gut microbiota may provide additional insights into the mechanisms.
Key messages: Maternal intakes of folic acid and/or choline can impact offspring's long-term health, with metabolic consequences that may arise from imbalances between folate and choline. However, there is a paucity of mechanistic understanding as various contri
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