HMGCR and obesity due to melanocortin 4 receptor deficiency: When looking at the effect of the FFC diet compared to the SD and FFC/SD diets, we found methylation changes in functionally relevant genes for obesity pathogenesis, e.g., the three hypermethylated genes involved in the lipid/cholesterol metabolic pathways, including HMGCR, LDLR, and MTTP. Indeed, deregulation of hepatic cholesterol metabolism plays an important role in the development and progression of obesity, especially for HMGCR and LDLR, which are the pivotal rate-limiting enzymes controlling cholesterol synthesis and homeostasis (Nestel et al., 1973).