Central and peripheral resistance to insulin and/or leptin signaling have been proposed as important mechanisms responsible for the deregulation of energy homeostasis, which may lead to obesity (Levin and Dunn-Meynell, 2002; Lustig et al., 2004; Esteghamati et al., 2009; Palou et al., 2010a) (see below). This evidence concerns the gene INS and obesity due to melanocortin 4 receptor deficiency.