Obesidad, inflamación y nutrición del hierro: estudio del porcentaje de metilación del DNA y expresión de microRNAs .

Abstract

Obesity is characterized by mild chronic inflammation that linked with diabetes mellitus and impaired iron homeostasis. Studies in human and murine show transgenerational epigenetic inheritance via the gametes to obesity, however, there are few studies investigating epigenetic changes in human sperm. Thus, the objective of this work was to study: the expression of microRNAs related to inflammation (miR-21 y miR-155) and iron nutrition (miR-122 and miR-200b) and mRNA expression of proinflammatory cytokines (IL-6 and TNF-) and hepcidin (HAMP). Also, the percentage of methylation in the promotor of IL-6, TNF-, HAMP and PDX-1 in peripheral mononuclear cells (PMC) and spermatozoa from normozoospermic obese (Ob; n= 17; BMI> 30 kg/m2) and lean (Cn; n= 17; BMI< 26 kg/m2) and subjects. Anthropometric measurements, biochemical profile and spermiogram were performed. The analyzes of microRNAs were performed using the Taqman assays. High Resolution Melting estimated the methylation percentage. The iron concentration in peripheral mononuclear cells (PMC); seminal plasma and spermatozoa was determined by ICP-MS. The results showed differences in weight, BMI and waist circumference between Ob and Cn subjects (p<0.0001). In the biochemical profile, higher values of basal glycemia (p=0.03), basal insulin (p=0.0005) and HOMA-IR (p=0.0006) were observed in the Ob group. In the parameters related to iron nutrition, were found differences in serum ferritin (p=0.03), serum Fe (p=0.007), iron content in seminal (p=0.04) plasma and spermatozoa (p=0.002). There were significant differences in the expression of TNF- (p=0.018), HAMP (p=0.03) and IL-6 (p=0.02) between Ob and Cn. In the Ob group a higher expression of miR-155 (p=0.02) and miR-21 (p=0.03) was observed in PMC and miR-122 (p=0.03) in plasma. In sperm, both miR-155 (p=0.004) and miR-122 (p=0.028) were also increased in the Ob group. There were no statistically significant differences in the methylation percentages of the genes related to inflammation, iron nutrition and glucose metabolism in peripheral mononuclear cells and/or spermatozoa. Our results show that a condition of obesity generates changes in both the expression profiles of microRNAs related to inflammation and iron nutrition at both the systemic and sperm levels.