Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism associated with body fat accumulation could possibly trigger an inflammatory process by elevating homocysteine levels and increasing cytokine production, causing several diseases. This study aimed to evaluate the effects of food intervention, and not folate supplements, on the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in overweight and obese women with the MTHFR C677T polymorphism. A randomized, double-blind eight-week clinical trial of 48 overweight and obese women was conducted. Participants were randomly assigned into two groups. They received 300 g of vegetables daily for eight weeks containing different doses of folate: 95 µg/day for Group 1 and 191 µg/day for Group 2. MTHFR C677T polymorphism genotyping was assessed by digestion with HinfI enzyme and on 12% polyacrylamide gels. Anthropometric measurements, 24-h dietary recall, and biochemical analysis (blood folic acid, vitamin B12, homocysteine (Hcy), TNF-α, IL-1β, and IL-6) were determined at the beginning and end of the study. Group 2 had a significant increase in folate intake (p < 0.001) and plasma folic acid (p < 0.05) for individuals with the cytosine–cytosine (CC), cytosine–thymine (CT), and thymine–thymine (TT) genotypes. However, only individuals with the TT genotype presented reduced levels of Hcy, TNF-α, IL-6, and IL-1β (p < 0.001). Group 1 showed significant differences in folate consumption (p < 0.001) and folic acid levels (p < 0.05) for individuals with the CT and TT genotypes. Food intervention with folate from vegetables increased folic acid levels and reduced interleukins, TNF-α, and Hcy levels, mainly for individuals with the TT genotype.

The study demonstrated the beneficial effect of folate intake in terms of a TAC elevation for the CC and TT genotypes of the MTHFR C677T polymorphism, an increase in folic acid levels for all genotypes, and a reduction in the Hcy levels for the TT genotype in response to an intervention consisting of an intake of 191 µg/d of folate supplied by vegetables.

Background Defects in DNA methylation have been shown to be associated with metabolic diseases such as obesity, dyslipidemia, and hypercholesterolemia. To analyze the methylation profile of the ADRB3 gene and correlate it with lipid profile, lipid intake, and oxidative stress based on malondialdehyde (MDA) and total antioxidant capacity (TAC), homocysteine and folic acid levels, nutritional status, lifestyle, and socioeconomic variables in an adult population. A cross-sectional epidemiological study representative of the East and West regions of the municipality of João Pessoa, Paraíba state, Brazil, enrolled 265 adults of both genders. Demographic, lifestyle, and socioeconomic questionnaires and a 24-h recall questionnaire were applied by trained interviewers’ home. Nutritional and biochemical evaluation (DNA methylation, lipid profile, MDA, TAC, homocysteine and folic acid levels) was performed. Results DNA hypermethylation of the ADRB3 gene, analyzed in leukocytes, was present in 50% of subjects and was associated with a higher risk of being overweight (OR 3.28; p = 0.008) or obese (OR 3.06; p = 0.017), a higher waist–hip ratio in males (OR 1.17; p = 0.000), greater intake of trans fats (OR 1.94; p = 0.032), higher LDL (OR 2.64; p = 0.003) and triglycerides (OR 1.81; p = 0.031), and higher folic acid levels (OR 1.85; p = 0.022). Conclusions These results suggest that epigenetic changes in the ADRB3 gene locus may explain the development of obesity and non-communicable diseases associated with trans-fat intake, altered lipid profile, and elevated folic acid. Because of its persistence, DNA methylation may have an impact in adults, in association with the development of non-communicable diseases. This study is the first population-based study of the ADRB3 gene, and the data further support evaluation of ADRB3 DNA methylation as an effective biomarker.

Obesity is highly prevalent in developed countries and contributes to a substantial burden of morbidity and mortality. Increased adiposity is often accompanied by comorbidities such as insulin resistance, type 2 diabetes, hypercholesterolemia, cardiovascular disease, fatty liver disease, low-grade inflammation, immune disorders, endocrine complications, and sleep apnea, which may require specific dietary and pharmacological interventions. The current obesity epidemic requires a better understanding of the underlying mechanisms through which genetic and epigenetic factors interact to determine metabolic characteristics. Epigenetic studies are dynamic; tags with reversible potential can be influenced by genetics and environment attributing phenotypic variations. There are large knowledge gaps regarding how human epigenetic changes are related to obesity and its consequences. Therefore, the present study elucidates the role of epigenetics in the etiology of obesity. Recent studies suggest that the epigenetic regulation of gene expression (DNA methylation and histone modifications) could be a major contributor to the variation of susceptibility to diseases such as obesity. The identification of genes that determine obesity susceptibility can provide information on the pathophysiological mechanisms underlying body weight regulation, food intake control and fat distribution, which in turn can lead to new approaches to treatment and prevention of obesity.

BackgroundObesity contributes to several cardiometabolic diseases, such as dyslipidemia, as a result of an unhealthy lifestyle and genetic factors. The methylation profile of genes involved in appetite control and metabolism, such as LEP (leptin) and POMC (proopiomelanocortin) and altered lipid levels can contribute to obesity, and these epigenetic changes have been associated with the effects of diet composition. The objective of this study was to evaluate the methylation levels of LEP and POMC genes and lipid profile values after intervention with dietary folate and hazelnut oil in overweight women.MethodsDouble-blind, placebo, controlled intervention study with 40 overweight adult women. Participants were randomized into four groups for 8 weeks: G1, 300 g of vegetables and 191 µg / day of folate and hazelnut oil; G2, 300 g of vegetables and 191 µg / day of folate and placebo; G3, 300 g of vegetables and 94 µg / day of folate and hazelnut oil; G4, the individuals were only accompanied. In addition to the levels of methylation, food consumption, anthropometric measurements, biochemical variables of lipid profile were evaluated.ResultsAfter the intervention, the participants presented reduction in the methylation levels of the studied genes in the three intervention groups in the LEP gene: G1 (p = 0.00), G2 (p = 0.00) and G3 (p = 0.00); in the POMC gene: G1 (p = 0.01), G2 (p = 0.02) and G3 (p = 0.01), and in the lipid profile, G1 reduced the levels of LDL-c (p = 0.04), HDL-c (p = 0.00) and Triglycerides (p = 0.04); in G3 there was a reduction in total cholesterol levels (p = 0.00), LDL-c (p = 0.00) and HDL-c (p = 0.00), and in G4 there was a reduction in total cholesterol values (p = 0.00), LDL-c (p = 0.00), HDL-c (p = 0.00) and triglycerides (p = 0.00), and also, an association in G2 between the POMC methylation levels with triglycerides (p = 0.00).ConclusionThe study provided evidence of a normocaloric intervention with dietary folate and hazelnut oil supplementation on the methylation levels of LEP and POMC genes and the role they can play in lipid metabolism.Trial registrationISRCTN, NCT04523532. Registered 21 August 2020, https://clinicaltrials.gov/ct2/show/NCT04523532