Decrease of the DNA methylation levels of the ADRB3 gene in leukocytes is related with serum folate in eutrophic adults.

BACKGROUND: DNA methylation has been evidenced as a potential epigenetic mechanism related to various candidate genes to development of obesity. Therefore, the objective of this study was to evaluate the DNA methylation levels of the ADRB3 gene by body mass index (BMI) in a representative adult population, besides characterizing this population as to the lipid profile, oxidative stress and food intake. METHODS: This was a cross-sectional population-based study, involving 262 adults aged 20-59 years, of both genders, representative of the East and West regions of the municipality of João Pessoa, Paraíba state, Brazil, in that were evaluated lifestyle variables and performed nutritional, biochemical evaluation and DNA methylation levels of the ADRB3 gene using high resolution melting method. The relationship between the study variables was performed using analyses of variance and multiple regression models. All results were obtained using the software R, 3.3.2. RESULTS: From the stratification of categories BMI, was observed a difference in the average variables values of age, waist-to-height ratio, waist-to-hip ratio, waist circumference, triglycerides and intake of trans fat, which occurred more frequently between the categories "eutrophic" and "obesity". From the multiple regression analysis in the group of eutrophic adults, it was observed a negative relationship between methylation levels of the ADRB3 gene with serum levels of folic acid. However, no significant relation was observed among lipid profile, oxidative stress and food intake in individuals distributed in the three categories of BMI. CONCLUSIONS: A negative relationship was demonstrated between methylation levels of the ADRB3 gene in eutrophic adults individuals with serum levels of folic acid, as well as with the independent gender of BMI, however, was not observed relation with lipid profile, oxidative stress and variables of food intake. Regarding the absence of relationship with methylation levels of the ADRB3 gene in the categories of overweight, mild and moderate obesity, the answer probably lies in the insufficient amount of body fat to initiate inflammatory processes and oxidative stress with a direct impact on methylation levels, what is differently is found most of the times in exacerbated levels in severe obesity.

The direct correlation between oxidative stress and LDL-C levels in adults is maintained by the Friedewald and Martin equations, but the methylation levels in the MTHFR and ADRB3 genes differ.

Low-density lipoprotein (LDL-C) concentrations are a standard of care in the prevention of cardiovascular disease and are influenced by different factors. This study compared the LDL-C concentrations estimated by two different equations and determined their associations with inflammatory status, oxidative stress, anthropometric variables, food intake and DNA methylation levels in the LPL, ADRB3 and MTHFR genes. A cross-sectional population-based study was conducted with 236 adults (median age 37.5 years) of both sexes from the municipality of João Pessoa, Paraíba, Brazil. The LDL-C concentrations were estimated according to the Friedewald and Martin equations. LPL, ADRB3 and MTHFR gene methylation levels; malondialdehyde levels; total antioxidant capacity; ultra-sensitive C-reactive protein, alpha-1-acid glycoprotein, homocysteine, cobalamin, and folic acid levels; usual dietary intake; and epidemiological variables were also determined. For each unit increase in malondialdehyde concentration there was an increase in the LDL-C concentration from 6.25 to 10.29 mg/dL (p <0.000). Based on the Martin equation (≥70 mg/dL), there was a decrease in the DNA methylation levels in the ADRB3 gene and an increase in the DNA methylation levels in the MTHFR gene (p <0.05). There was a positive relation of homocysteine and cholesterol intake on LDL-C concentrations estimated according to the Friedewald equation and of waist circumference and age based on the two estimates. It is concluded the LDL-C concentrations estimated by the Friedewald and Martin equations were different, and the Friedewald equation values were significantly lower than those obtained by the Martin equation. MDA was the variable that was most positively associated with the estimated LDL-C levels in all multivariate models. Significant relationships were observed based on the two estimates and occurred for most variables. The methylation levels of the ADRB3 and MTHFR genes were different according to the Martin equation at low LDL-C concentrations (70 mg/dL).

α-Tocopherol influences glycaemic control and miR-9-3 DNA methylation in overweight and obese women under an energy-restricted diet: a randomized, double-blind, exploratory, controlled clinical trial.

BACKGROUND: Excess weight is a strong risk factor for the development of dysglycaemia. It has been suggested that changes in the metabolism microRNAs, small non-coding RNAs that regulate gene expression, could precede late glycaemic changes. Vitamin E in turn may exert important functions in methylation and gene expression processes. This study aimed to determine the effect of α-tocopherol on glycaemic variables and miR-9-1 and miR-9-3 promoter DNA methylation in overweight women. METHODS: A randomized, double-blind, exploratory, placebo-controlled study was conducted in overweight and obese adult women (n = 44) who ingested synthetic vitamin E (all-rac-α-tocopherol), natural source vitamin E (RRR-rac-α-tocopherol) or placebo capsules and were followed up for a period of 8 weeks. Supplemented groups also received dietary guidance for an energy-restricted diet. An additional group that received no supplementation and did not follow an energy-restricted diet was also followed up. The intervention effect was evaluated by DNA methylation levels (quantitative real-time PCR assay) and anthropometric and biochemical variables (fasting plasma glucose, haemoglobin A1C, insulin, and vitamin E). RESULTS: Increased methylation levels of the miR-9-3 promoter region (P < 0.001) and reduced haemoglobin A1C (P < 0.05) were observed in the natural source vitamin E group after intervention. Increased fasting plasma glucose was observed in the synthetic vitamin E group, despite the significant reduction of anthropometric variables compared to the other groups. CONCLUSIONS: α-Tocopherol from natural sources increased methylation levels of the miR-9-3 promoter region and reduced haemoglobin A1C in overweight women following an energy-restricted diet. These results provide novel information about the influence of vitamin E on DNA methylation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02922491. Registered 4 October, 2016.