Interestingly, the modulation of hypothalamic SIRT1 has been implicated in the reduction of leptin resistance as a strategy for treating obesity [49,50], and the activation of SIRT1 by resveratrol improves peripheral and central leptin signaling and reverses leptin resistance caused by diet-induced obesity [51]. Here, SIRT1 is linked to obesity due to melanocortin 4 receptor deficiency.