In a diet-induced obesity model, Dnmt1 and Dnmt3a mRNA expression, described as an epigenetic mediator of insulin resistance, was elevated but could be significantly reduced after insulin treatment.28 The DR severity and inflammatory pathways,29 higher levels of total cholesterol and LDL cholesterol30 and physical activity31 were associated with MTHFR gene promoter hypermethylation. This evidence concerns the gene INS and obesity due to melanocortin 4 receptor deficiency.