In the ARC, it is deeply involved in the control of energy homeostasis and in the diet-dependent modulation of reproduction via the epigenetic modulation of Kiss1. Sirt1-sex specific protecting roles against high-fat-induced obesity and metabolic derangements has been reported suggesting that dietary supplementation with natural phytochemical compounds like polyphenols, which are capable of modulating Sirt1 activity, may be useful to preserve Sirt1 activity. Here, SIRT1 is linked to obesity due to melanocortin 4 receptor deficiency.