In the course of diet-induced obesity (DIO), orexin-A represses satiety-promoting pro-opiomelanocortin (POMC) neurons in the hypothalamic arcuate nucleus (ARC) by eCB-mediated activation of postsynaptic CB1 on POMC neurons (Morello et al., 2016). This evidence concerns the gene CNR1 and obesity due to melanocortin 4 receptor deficiency.