Specifically, its activity increases in the hypothalamus during fasting, while deletion of Sirt1 in mice in pro-opiomelanocortin (POMC) hypothalamic neurons decreases energy expenditure and increases susceptibility to diet-induced obesity, whereas its deletion in Agouti-related peptide (AgRP) neurons has the opposite effect (81). This evidence concerns the gene POMC and obesity due to melanocortin 4 receptor deficiency.