We propose that hypermethylation of GR and FKBP5, key HPA axis-regulatory genes, is associated with metabolic dysfunction and that assessing methylation patterns of GR and FKBP5 in GSAT and ASAT depots may provide a better understanding of the intrinsic differences between abdominal and lower body obesity. This evidence concerns the gene FKBP5 and obesity due to melanocortin 4 receptor deficiency.