As observed with AMPK, the anatomical location of SIRT1 in the hypothalamus is relevant for the protection against diet-induced obesity: although SIRT in POMC neurons is required for normal BAT-like remodeling in the perigonadal fat depot [73], SIRT1 in SF1 neurons controls insulin sensitivity in the skeletal muscle [57] (Figure 3). This evidence concerns the gene PRKAA2 and obesity due to melanocortin 4 receptor deficiency.