While some studies have suggested that cAMP in MC4R-expressing PVN neurons plays a role in the regulation of food intake and body weight (47, 48), many MC4R mutations linked to human obesity do not show defects in Gsα/cAMP signaling (22, 23, 49), suggesting that alternative MC4R signaling pathways may also be involved in the normal maintenance of energy balance. The gene discussed is GNAS; the disease is obesity due to melanocortin 4 receptor deficiency.