Higher Fruit Intake Is Related to TNF-α Hypomethylation and Better Glucose Tolerance in Healthy Subjects.

BACKGROUND/AIM: This study hypothesized an association between healthy dietary patterns, hypermethylation of the tumor necrosis factor-α (TNF-α) promoter and decreased risk of metabolic changes. METHODS: Forty normal-weight young women were involved in this cross-sectional study. DNA was isolated from white blood cells, and CpG site methylation in TNF-α was analyzed by Sequenom EpiTyper. The quality of the diet was assessed by Healthy Eating Index (HEI-2005). RESULTS: Contradicting our hypothesis, HEI-2005 score was negatively associated with CpG5 (r = -0.460, p = 0.003) and TNF-α total methylation (r = -0.355, p = 0.026). A higher intake of fruits was related to lower insulin, HOMA-IR, and TNF-α methylation. No other dietary pattern was related to TNF-α methylation. TNF-α total methylation correlated positively with systolic blood pressure (r = 0.323; p = 0.042) and CpG5 methylation with body mass index (r = 0.333, p = 0.036). Furthermore, fiber intake was negatively associated with the CpG5 (r = -0.324, p = 0.041) and TNF-α total methylation (r = -0.434, p = 0.005), whereas vitamin C intake was negatively associated with TNF-α total methylation (r = -0.411, p = 0.009). Intakes of apples and citrus fruits were negatively associated with TNF-α total methylation. CONCLUSION: A healthy dietary pattern and higher fruit intake (particularly apples and citrus fruits) were related to better glucose tolerance in healthy subjects, which could be mediated by lower TNF-α methylation.

LINE-1 methylation is positively associated with healthier lifestyle but inversely related to body fat mass in healthy young individuals.

With the goal of investigating if epigenetic biomarkers from white blood cells (WBC) are associated with dietary, anthropometric, metabolic, inflammatory and oxidative stress parameters in young and apparently healthy individuals. We evaluated 156 individuals (91 women, 65 men; age: 23.1±3.5 years; body mass index: 22.0±2.9 kg/m(2)) for anthropometric, biochemical and clinical markers, including some components of the antioxidant defense system and inflammatory response. DNA methylation of LINE-1, TNF-α and IL-6 and the expression of some genes related to the inflammatory process were analyzed in WBC. Adiposity was lower among individuals with higher LINE-1 methylation. On the contrary, body fat-free mass was higher among those with higher LINE-1 methylation. Individuals with higher LINE-1 methylation had higher daily intakes of calories, iron and riboflavin. However, those individuals who presented lower percentages of LINE-1 methylation reported higher intakes of copper, niacin and thiamin. Interestingly, the group with higher LINE-1 methylation had a lower percentage of current smokers and more individuals practicing sports. On the other hand, TNF-α methylation percentage was negatively associated with waist girth, waist-to-hip ratio and waist-to-stature ratio. Plasma TNF-α levels were lower in those individuals with higher TNF-α methylation. This study suggests that higher levels of LINE-1 and TNF-α methylation are associated with better indicators of adiposity status in healthy young individuals. In addition, energy and micronutrient intake, as well as a healthy lifestyle, may have a role in the regulation of DNA methylation in WBC and the subsequent metabolic changes may affect epigenetic biomarkers.

DNA Methylation and Hydroxymethylation Levels in Relation to Two Weight Loss Strategies: Energy-Restricted Diet or Bariatric Surgery.

BACKGROUND: Weight loss can be influenced by genetic factors and epigenetic mechanisms that participate in the regulation of body weight. This study aimed to investigate whether the weight loss induced by two different obesity treatments (energy restriction or bariatric surgery) may affect global DNA methylation (LINE-1) and hydroxymethylation profile, as well as the methylation patterns in inflammatory genes. METHODS: This study encompassed women from three differents groups: 1. control group (n = 9), normal weight individuals; 2. energy restriction group (n = 22), obese patients following an energy-restricted Mediterranean-based dietary treatment (RESMENA); and 3. bariatric surgery group (n = 14), obese patients underwent a hypocaloric diet followed by bariatric surgery. Anthropometric measurements and 12-h fasting blood samples were collected before the interventions and after 6 months. Lipid and glucose biomarkers, global hydroxymethylation (by ELISA), LINE-1, SERPINE-1, and IL-6 (by MS-HRM) methylation levels were assessed in all participants. RESULTS: Baseline LINE-1 methylation was associated with serum glucose levels whereas baseline hydroxymethylation was associated with BMI, waist circumference, total cholesterol, and triglycerides. LINE-1 and SERPINE-1 methylation levels did not change after weight loss, whereas IL-6 methylation increased after energy restriction and decreased in the bariatric surgery group. An association between SERPINE-1 methylation and weight loss responses was found. CONCLUSIONS: Global DNA methylation and hydroxymethylation might be biomarkers for obesity and associated comorbidities. Depending on the obesity treatment (diet or surgery), the DNA methylation patterns behave differently. Baseline SERPINE-1 methylation may be a predictor of weight loss values after bariatric surgery.