POMC and obesity due to melanocortin 4 receptor deficiency: On the other hand, conditional knockout of SIRT1 in POMC neurons (loxP-flanked exon 4 of Sirt1 with Cre recombinase driven by the Pomc promoter) was shown to reduce energy expenditure and increase susceptibility to diet-induced obesity, as well as signaling processes induced by the satiety hormone leptin (Ramadori et al., 2010).