LEP and obesity due to melanocortin 4 receptor deficiency: Interestingly, a recent study conducted by Tam et al. indicated that a peripheral inhibition of CB1R in mice with diet-induced obesity (DIO) leads to an increase in the leptin sensitivity, which results in hypophagia via the reactivation of melanocortin signaling in the arcuate nucleus (ARC) in the hypothalamus [33].