We reported that hyperphagia and increased meal size associated with WD-induced obesity in mice are dependent on (i) elevated levels of endocannabinoids in the upper small-intestinal epithelium and (ii) CB1R-mediated inhibition of nutrient-induced signaling of the satiation peptide, cholecystokinin [16]. Here, CNR1 is linked to obesity due to melanocortin 4 receptor deficiency.