Abnormal DNA methylations of key metabolic-related genes, such as Leptin (Houde et al, 2015), adiponectin (Houde et al, 2015), PGC1α (Brons et al, 2010), IGF-2 (Perkins et al, 2012), appetite-related genes-(POMC (Crujeiras et al, 2013), NPY (Crujeiras et al, 2013)), are frequently implicated in the development of obesity and insulin resistance. Here, PPARGC1A is linked to obesity due to melanocortin 4 receptor deficiency.