Interestingly, the metabolic actions of melanocortin (MCH) are reduced in mice lacking Sirt1, specifically in POMC neurons, revealing that the Sirt1/FoxO1 pathway also regulates the inhibitory effect of MCH on POMC expression, thus mediating MCH-induced feeding, adiposity, and glucose intolerance [90], and confirming the relevance of Sirt1 activity in obesity. This evidence concerns the gene PMCH and obesity due to melanocortin 4 receptor deficiency.