Importantly, the hypothalamic actions of SIRT1 are not restricted to ARC neuronal populations; thus, ablation of SIRT1 in SF1 neurons, abundantly expressed in the VMH, is bound to metabolic perturbations, while over-expression of SIRT1 in this neuronal population protects from diet-induced obesity and insulin resistance (44). Here, SIRT1 is linked to obesity due to melanocortin 4 receptor deficiency.