Leticia Goni

Single-nucleotide polymorphisms and Dna methylation markers associated with central obesity and regulation of body weight

Visceral fat is strongly associated with the development of specific obesity-related metabolic alterations. Genetic and epigenetic mechanisms seem to be involved in the development of obesity and visceral adiposity. The aims of this review are to identify the single-nucleotide polymorphisms related to central obesity and to summarize the main findings on DNA methylation and obesity. A search of the MEDLINE database was conducted to identify genome-wide association studies, meta-analyses of genome-wide association studies, and gene-diet interaction studies related to central obesity, and, in addition, studies that analyzed DNA methylation in relation to body weight regulation. A total of 8 genome-wide association studies and 9 meta-analyses of genome-wide association studies reported numerous single-nucleotide polymorphisms to be associated with central obesity. Ten studies analyzed gene-diet interactions and central obesity, while 2 epigenome-wide association studies analyzed DNA methylation patterns and obesity. Nine studies investigated the relationship between DNA methylation and weight loss, excess body weight, or adiposity outcomes. Given the development of new sequencing and omics technologies, significantly more knowledge on genomics and epigenomics of obesity and body fat distribution will emerge in the near future.

Guide for Current Nutrigenetic, Nutrigenomic, and Nutriepigenetic Approaches for Precision Nutrition Involving the Prevention and Management of Chronic Diseases Associated with Obesity

Chronic diseases, including obesity, are major causes of morbidity and mortality in most countries. The adverse impacts of obesity and associated comorbidities on health remain a major concern due to the lack of effective interventions for prevention and management. Precision nutrition is an emerging therapeutic approach that takes into account an individuals genetic and epigenetic information, as well as age, gender, or particular physiopathological status. Advances in genomic sciences are contributing to a better understanding of the role of genetic variants and epigenetic signatures as well as gene expression patterns in the development of diverse chronic conditions, and how they may modify therapeutic responses. This knowledge has led to the search for genetic and epigenetic biomarkers to predict the risk of developing chronic diseases and personalizing their prevention and treatment. Additionally, original nutritional interventions based on nutrients and bioactive dietary compounds that can modify epigenetic marks and gene expression have been implemented. Although caution must be exercised, these scientific insights are paving the way for the design of innovative strategies for the control of chronic diseases accompanying obesity. This document provides a number of examples of the huge potential of understanding nutrigenetic, nutrigenomic, and nutriepigenetic roles in precision nutrition.

Gene-Gene Interplay and Gene-Diet Interactions Involving the MTNR1B rs10830963 Variant with Body Weight Loss

Background/Aims: Investigation of the genetic makeup may facilitate the implementation of more personalized nutritional interventions. The aims were to examine whether the rs10830963 MTNR1B polymorphism affects weight loss in response to a hypocaloric diet and to find potential gene-gene interplays and gene-diet interactions. Methods: 167 subjects enrolled in a personalized nutritional intervention for weight loss (3-6 weeks) were examined for anthropometric measurements, dietary habits and physical activity at baseline and at the first follow-up visit. Three polymorphisms, which have previously been associated with body weight regulation, rs10830963 (MTNR1B), rs9939609 (FTO) and rs17782313 (MC4R), were analyzed using the Luminex® 100/200™ System. Results: After adjusting for covariates, females with the rs10830963 CG/GG genotype showed lower weight loss than those with the CC genotype. In the total population, carriers of variant alleles of both FTO and MC4R showed a significant association with MTNR1B and weight loss outcome. Moreover, among women, higher total protein and animal protein intakes were associated with a lower weight loss in G allele carriers of the MTNR1B variant. Conclusions: Our data evidenced that rs10830963 MTNR1B polymorphism could be associated with individual differences in weight loss induced by a hypocaloric diet. This association was influenced by FTO and MC4R loci and modified by baseline protein intake.

Parity implications for anthropometrical variables, lifestyle behaviors and dietary habits in pregnant women

BACKGROUND Maintaining an adequate health status and appropriate lifestyles during pregnancy is of great importance to prevent adverse outcomes for both mother and baby. The present study aimed to assess the nutritional status, socio-demographic features, lifestyle behaviors and dietary habits of pregnant women in Spain, and to identify the influence of parity on these profiles. METHODS This cross-sectional study included pregnant women from regions all over Spain. The information was collected through a 40 item questionnaire, previously validated by community health professionals. RESULTS The 5,087 pregnant women analyzed had an average age of 31.9 years with an adequate nutritional status. The distribution of the sample was 56% nulliparous and 44% multiparous. The nulliparous reported a better self-perceived health status and nutritional balance, and a lower incidence of gestational diabetes mellitus. However, the multiparous showed healthier lifestyle habits (lower rates of smoking and alcohol consumption) and more physically active patterns. Regarding diet, nulliparous pregnant women consumed more dairy products, fresh fruit and nuts, and less bread, rice/pasta/potatoes, meat, sausage and buns/pastries than multiparous pregnant women. CONCLUSIONS Differences between analyzed patterns were observed in anthropometrical variables, lifestyle behaviors and dietary habits, which may require different nutritional messages to nulliparous as compared to multiparous from a public health point of view.

Macronutrient-specific effect of the MTNR1B genotype on lipid levels in response to 2 year weight-loss diets

Compelling evidence indicates that lipid metabolism is in partial control of the circadian system. In this context, it has been reported that the melatonin receptor 1B (MTNR1B) genetic variant influences the dynamics of melatonin secretion, which is involved in the circadian system as a chronobiotic. The objective was to analyze whether the MTNR1B rs10830963 genetic variant was related to changes in lipid levels in response to dietary interventions with different macronutrient distribution in 722 overweight/obese subjects from the POUNDS Lost trial. We did not find a significant association between the MTNR1B genotype and changes in lipid metabolism. However, dietary fat intake significantly modified genetic effects on 2 year changes in total and LDL cholesterol (P interaction = 0.006 and 0.001, respectively). In the low-fat diet group, carriers of the sleep disruption G allele (minor allele) showed a greater reduction of total cholesterol (β ± SE = −5.78 ± 2.88 mg/dl, P = 0.04) and LDL cholesterol (β ± SE = −7.19 ± 2.37 mg/dl, P = 0.003). Conversely, in the high-fat diet group, subjects carrying the G allele evidenced a smaller decrease in total cholesterol (β ± SE = 5.81 ± 2.65 mg/dl, P = 0.03) and LDL cholesterol (β ± SE = 5.23 ± 2.21 mg/dl, P = 0.002). Subjects carrying the G allele of the circadian rhythm-related MTNR1B variant may present a bigger impact on total and LDL cholesterol when undertaking an energy-restricted low-fat diet.

Effect of the interaction between diet composition and the PPM1K genetic variant on insulin resistance and β cell function markers during weight loss: results from the Nutrient Gene Interactions in Human Obesity: implications for dietary guidelines (NUGENOB) randomized trial

Background: Circulating branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs) have been shown to be associated with insulin resistance and diabetes risk. The common rs1440581 T allele in the protein phosphatase Mg2+/Mn2+ dependent 1K (PPM1K) gene has been related to elevated BCAA concentrations and risk of type 2 diabetes.Objective: In the present study, we tested whether dietary fat and carbohydrate intakes influenced the association between the rs1440581 PPM1K genetic variant and glucose-metabolism traits during weight loss.Design: The rs1440581 PPM1K genetic variant was genotyped in a total of 757 nondiabetic individuals who were randomly assigned to 1 of 2 energy-restricted diets that differed in macronutrient composition (low-fat diet: 20-25% fat, 15% protein, and 60-65% carbohydrate; high-fat diet: 40-45% fat, 15% protein, and 40-45% carbohydrate). The changes in fasting glucose, fasting insulin, insulin resistance (homeostasis model assessment of insulin resistance) and homeostasis model assessment of β cell function (HOMA-B) were measured after a mean ± SD weight loss of 6.8 ± 3.4 kg over 10 wk and analyzed according to the presence of the T allele of rs1440581.Results: The rs1440581 T allele was associated with a smaller improvement in glucose concentrations after the 10-wk dietary intervention (β ± SE: 0.05 ± 0.02 mg/dL; P = 0.03). In addition, significant gene-diet interactions were shown for the rs1440581 PPM1K genetic variant in relation to changes in insulin and HOMA-B (P-interaction = 0.006 and 0.002, respectively). In response to the high-fat diet, the T allele was associated with a higher reduction of insulin (β ± SE: -0.77 ± 0.40 μU/mL; P = 0.04) and HOMA-B (β ± SE: -13.2 ± 3.81; P = 0.003). An opposite effect was observed in the low-fat diet group, although in this group the T allele was marginally (P = 0.10) and not significantly (P = 0.24) associated with insulin and HOMA-B, respectively.Conclusion:PPM1K rs1440581 may affect changes in glucose metabolism during weight loss, and this effect is dependent on dietary fat and carbohydrate intakes. This trial was registered at controlled-trials.com as ISRCTN25867281.

Sociodemographic and dietary profile of 4,471 childbearing-age women planning a pregnancy

BACKGROUND The maintenance of healthy lifestyles is of great importance to prevent pregnancy-related diseases at early stages. For this reason, the knowledge of the overall wellbeing of women at childbearing-age is necessary to provide appropriate advice to maintain or improve the nutritional status. The aim of this research was to assess the lifestyles of childbearing-age women planning a pregnancy and to examine the difference between primiparae and multiparae women on these lifestyles. METHODS This cross-sectional survey involved 4,471 Spanish women at childbearing-age that were planning a pregnancy. Information was collected through a questionnaire by community health professionals. RESULTS The profile of childbearing-age recruited women planning a pregnancy were in her early thirties (31.4 ± 4.8 years) and 72.5% were seeking for her first baby. They had a good self-perception of their nutritional and health status and followed a balanced diet. Interestingly, primiparae women had lower risk of health complications but they were greater consumers of tobacco and alcohol (p < 0.001), and consumed less fortified milk, iodine and iron supplements than multiparae women. Additionally, the examined population showed a more sedentary pattern in primiparae women as compared to the remaining group concerning hours/day lying, sitting and standing. CONCLUSION Differences between both preconceptional conditions (primiparae and multiparae women) bring a great opportunity to promote healthy habits among childbearing- aged women, according to the personal profile, in order to prevent burdens in future pregnancies underlying modifiable or preventable factors.

Phenotype and genotype predictors of BMI variability among European adults

Background/ObjectiveObesity is a complex and multifactorial disease resulting from the interactions among genetics, metabolic, behavioral, sociocultural and environmental factors. In this sense, the aim of the present study was to identify phenotype and genotype variables that could be relevant determinants of body mass index (BMI) variability.Subjects/MethodsIn the present study, a total of 1050 subjects (798 females; 76%) were included. Least angle regression (LARS) analysis was used as regression model selection technique, where the dependent variable was BMI and the independent variables were age, sex, energy intake, physical activity level, and 16 polymorphisms previously related to obesity and lipid metabolism.ResultsThe LARS analysis obtained the following formula for BMI explanation: (64.7 + 0.10 × age [years] + 0.42 × gender [0, men; 1, women] + −40.6 × physical activity [physical activity level] + 0.004 × energy intake [kcal] + 0.74 × rs9939609 [0 or 1–2 risk alleles] + −0.72 × rs1800206 [0 or 1–2 risk alleles] + −0.86 × rs1801282 [0 or 1–2 risk alleles] + 0.87 × rs429358 [0 or 1–2 risk alleles]. The multivariable regression model accounted for 21% of the phenotypic variance in BMI. The regression model was internally validated by the bootstrap method (r2 original data set = 0.208, mean r2 bootstrap data sets = 0.210).ConclusionIn conclusion, age, physical activity, energy intake and polymorphisms in FTO, APOE, PPARG and PPARA genes are significant predictors of the BMI trait.

Association of the Gly482Ser PPARGC1A gene variant with different cholesterol outcomes in response to two energy-restricted diets in subjects with excessive weight

OBJECTIVES The aim of this study was to investigate the influence of two PPARGC1A gene polymorphisms on metabolic outcomes in response to two energy-restricted diets. METHODS A 4-mo nutritional intervention was conducted that involved two different hypo-energetic diets based on low-fat (LF) and moderately high-protein (MHP) dietary patterns. Unrelated subjects with excessive weight were genotyped for two PPARGC1A polymorphisms: Rs8192678 (Gly482Ser) and rs3755863 (G > A). Genotyping was performed by next-generation sequencing and haplotypes were screened. Anthropometric measurements and biochemical tests were assessed with standardized methods. RESULTS Different cholesterol outcomes were observed by diet and Gly482Ser genotype. The Gly482 Gly homozygotes after an LF diet had lower reductions in total cholesterol (-9 mg/dL vs. -27 mg/dL; P = 0.017) and low-density lipoprotein cholesterol levels (-5 mg/dL vs. -18 mg/dL; P = 0.016) than the subjects who were carriers of 482 Ser allele. However, this finding was not recorded in the MHP group where Gly482 Gly homozygotes underwent similar cholesterol decreases as the 482 Ser allele carriers. Likewise, all genotype carriers had significant reductions in the frequencies of hypercholesterolemia (total cholesterol ≥200 mg/dL) except for Gly482 Gly homozygotes in the LF group. Meanwhile, the rs3755863 polymorphism and PPARGC1A haplotypes showed borderline effects with regard to cholesterol decreases. CONCLUSIONS An energy-restricted MHP diet might be more beneficial than an LF diet to reduce serum cholesterol among subjects who are carriers of the PPARGC1A Gly482Gly genotype. The analysis of this genetic variant might be the basis for a precise, nutrigenetic management of hypercholesterolemia based on genetic makeup.

Interaction between an ADCY3 Genetic Variant and Two Weight-Lowering Diets Affecting Body Fatness and Body Composition Outcomes Depending on Macronutrient Distribution: A Randomized Trial

The adenylate cyclase 3 (ADCY3) gene is involved in the regulation of several metabolic processes including the development and function of adipose tissue. The effects of the ADCY3 rs10182181 genetic variant on changes in body composition depending on the macronutrient distribution intake after 16 weeks of the dietary intervention were tested. The ADCY3 genetic variant was genotyped in 147 overweight or obese subjects, who were randomly assigned to one of the two diets varying in macronutrient content: a moderately-high-protein diet and a low-fat diet. Anthropometric and body composition measurements (DEXA scan) were recorded. Significant interactions between the ADCY3 genotype and dietary intervention on changes in weight, waist circumference, and body composition were found after adjustment for covariates. Thus, in the moderately-high-protein diet group, the G allele was associated with a lower decrease of fat mass, trunk and android fat, and a greater decrease in lean mass. Conversely, in the low-fat diet group carrying the G allele was associated with a greater decrease in trunk, android, gynoid, and visceral fat. Subjects carrying the G allele of the rs10182181 polymorphism may benefit more in terms of weight loss and improvement of body composition measurements when undertaking a hypocaloric low-fat diet as compared to a moderately-high-protein diet.