Estudio de asociación epigenómica en la pérdida de peso tras una intervención nutricional: Estudio RESMENA.

Through anepigenomics approach, the possible association between baseline levels in DNA methylation and a better weight loss response after a multidisciplinary intervention program were analyzedin obese population from RESMENA-S study. Three DNA regions that are differentially methylated (RGS6, A2BP1 and RASGRF1 genes) showed differential methylation levels at baseline between high and low responders to the multidisciplinary weight loss intervention. Moreover, these genes were implicated in the same metabolic pathway and have been previously significantly associated with obesity.Mediante una aproximación epigenómica, se analizaron las posibles asociaciones entre los niveles basales en la metilación del ADN y una mejor respuesta a la pérdida de peso después de un programa de intervención nutricional en la población obesa del estudio RESMENA. Esta investigación ha identificado 3 regiones de ADN (genes RGS6, A2BP1 y RASGRF1) que se encuentran diferencialmente metiladas entre sujetos con alta y baja respuesta a la pérdida de peso. Además, estos genes están implicados en la misma ruta metabólica y habían sido previamente significativamente asociados con la obesidad

Common Variants of the Liver Fatty Acid Binding Protein Gene Influence the Risk of Type 2 Diabetes and Insulin Resistance in Spanish Population

SummaryThe main objective was to evaluate the association between SNPs and haplotypes of the FABP1-4 genes and type 2 diabetes, as well as its interaction with fat intake, in one general Spanish population. The association was replicated in a second population in which HOMA index was also evaluated.Methods1217 unrelated individuals were selected from a population-based study [Hortega study: 605 women; mean age 54 y; 7.8% with type 2 diabetes]. The replication population included 805 subjects from Segovia, a neighboring region of Spain (446 females; mean age 52 y; 10.3% with type 2 diabetes). DM2 mellitus was defined in a similar way in both studies. Fifteen SNPs previously associated with metabolic traits or with potential influence in the gene expression within the FABP1-4 genes were genotyped with SNPlex and tested. Age, sex and BMI were used as covariates in the logistic regression model.ResultsOne polymorphism (rs2197076) and two haplotypes of the FABP-1 showed a strong association with the risk of DM2 in the original population. This association was further confirmed in the second population as well as in the pooled sample. None of the other analyzed variants in FABP2, FABP3 and FABP4 genes were associated. There was not a formal interaction between rs2197076 and fat intake. A significant association between the rs2197076 and the haplotypes of the FABP1 and HOMA-IR was also present in the replication population.ConclusionsThe study supports the role of common variants of the FABP-1 gene in the development of type 2 diabetes in Caucasians

Expression of inflammation-related miRNAs in white blood cells from subjects with metabolic syndrome after 8 wk of following a Mediterranean diet–based weight loss program

The aim of this study was to evaluate the influence of a dietary strategy for weight loss (the RESMENA [reduction of metabolic syndrome in Navarra, Spain] diet) on the expression of inflammation-related microRNAS (miRNAs) and genes in white blood cells (WBC) from individuals with metabolic syndrome (MetS). The clinical, anthropometric, and biochemical characteristics of 40 individuals with MetS (20 men and 20 women; age: 48.84 ± 10.02 y; body mass index: 35.41 ± 4.42 kg/m2) were evaluated before and after an 8-wk hypocaloric diet based on the Mediterranean dietary pattern. Nutrient intake was assessed with a food frequency questionnaire and 48-h weighed food records. Total RNA was isolated from WBC and the expression of some inflammation-related miRNAs and mRNAs (IL-6, TNF-α, ICAM-1, IL-18, SERPINE1, VCAM-1, GAPDH) was assessed by quantitative polymerase chain reaction. The RESMENA nutritional intervention improved most anthropometric and biochemical features. The expression of miR-155-3p was decreased in WBC, whereas Let-7b was strongly upregulated as a consequence of the dietary treatment. However, they were not correlated with the expression of the proinflammatory genes in the same cells. The changes in the expression of let-7b, miR-125b, miR-130a, miR-132-3p, and miR-422b were significantly associated with changes in diet quality when assessed by the Healthy Eating Index. Moreover, low consumption of lipids and saturated fat (g/d) were associated with higher expression of let-7b after the nutritional intervention. The Mediterranean-based nutritional intervention was able to induce changes in the expression of let-7b and miR-155-3p in WBC from patients with MetS after 8 wk. Moreover, the quality of the diet has an important effect on the miRNAs expression changes. These results should be highlighted because these miRNAs have been associated with inflammatory gene regulation and important human diseases

Higher fruit intake is related to TNF-? 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-? (TNF-?) promoter and decreased risk of metabolic changes. Methods: Forty normal-weight young women were involved in this crosssectional study. DNA was isolated from white blood cells, and CpG site methylation in TNF-? 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-? total methylation (r = ?0.355, p = 0.026). A higher intake of fruits was related to lower insulin, HOMA-IR, and TNF-? methylation. No other dietary pattern was related to TNF-? methylation. TNF-? 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-? total methylation (r = ?0.434, p = 0.005), whereas vitamin C intake was negatively associated with TNF-? total methylation (r = ?0.411, p = 0.009). Intakes of apples and citrus fruits were negatively associated with TNF-? 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-? methylation

LINE-1 and inflammatory gene methylation levels are early biomarkers of metabolic changes : association with adiposity.

We analyzed whether global and inflammatory genes methylation can be early predictors of metabolic changes and their associations with the diet, in a cross-sectional study (n?40). Higher global methylation was associated to adiposity, insulin resistance, and lower quality of the diet. Methylation of IL-6, SERPINE1 and CRP genes was related to adiposity traits and macronutrients intake. SERPINE1 hypermethylation was also related to some metabolic alterations. CRP methylation was a better predictor of insulin resistance than CRP plasma concentrations. Global and inflammatory gene promoter hypermethylation can be good early biomarkers of adiposity and metabolic changes and are associated to the quality of the diet

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

<p>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/m²) for anthropometric, biochemical and clinical markers, including some components of the antioxidant defense system and inflammatory response. DNA methylation of <i>LINE-1, TNF-</i>α and <i>IL-6</i> and the expression of some genes related to the inflammatory process were analyzed in WBC. Adiposity was lower among individuals with higher <i>LINE-1</i> methylation. On the contrary, body fat-free mass was higher among those with higher <i>LINE-1</i> methylation. Individuals with higher <i>LINE-1</i> methylation had higher daily intakes of calories, iron and riboflavin. However, those individuals who presented lower percentages of <i>LINE-1</i> methylation reported higher intakes of copper, niacin and thiamin. Interestingly, the group with higher <i>LINE-1</i> methylation had a lower percentage of current smokers and more individuals practicing sports. On the other hand, <i>TNF-</i>α methylation percentage was negatively associated with waist girth, waist-to-hip ratio and waist-to-stature ratio. Plasma <i>TNF-</i>α levels were lower in those individuals with higher <i>TNF-</i>α methylation. This study suggests that higher levels of <i>LINE-1</i> and <i>TNF-</i>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.</p

<i>LINE-1</i> and inflammatory gene methylation levels are early biomarkers of metabolic changes: association with adiposity

<p>We analyzed whether global and inflammatory genes methylation can be early predictors of metabolic changes and their associations with the diet, in a cross-sectional study (<i>n</i> = 40). Higher global methylation was associated to adiposity, insulin resistance, and lower quality of the diet. Methylation of <i>IL-6, SERPINE1</i> and <i>CRP</i> genes was related to adiposity traits and macronutrients intake. <i>SERPINE1</i> hypermethylation was also related to some metabolic alterations. <i>CRP</i> methylation was a better predictor of insulin resistance than CRP plasma concentrations. Global and inflammatory gene promoter hypermethylation can be good early biomarkers of adiposity and metabolic changes and are associated to the quality of the diet.</p

General characteristics of the studied subjects.

<p> <i>Values are mean ± standard deviation or absolute number (percentage); NA: Not available.</i></p>*<p> <i>Significant differences between the two populations p-value<0.05.</i></p>**<p> <i>Significant differences between the two populations, p-value<0.01.</i></p>***<p> <i>Significant differences between the two populations, p-value<0.001.</i></p>1<p> <i>This information was available for 1427 subjects.</i></p>2<p> <i>This information was available for 210 subjects.</i></p

Individual SNPs and haplotypes association with HOMA index in Segovia population.

<p>ALL^¶ does not included those 31 diabetics under treatment; <i>CHR: chromosome; A1: minor allele; OR: odds ratio;</i></p>*<p> <i>Confidence interval for the OR or beta parameter;</i></p>**<p> <i>p-value after Bonferroni correction:</i></p>***<p> <i>Haplotype frequency; ADD: additive model; DOM: dominant, REC: recessive.</i></p