To further explore the role of MC4R signaling pathways in the regulation of energy balance, we examined in detail the physiological consequences in mice and signaling properties of one mutant MC4R that is associated with early-onset obesity in humans and has been reported to have relatively intact Gsα signaling (MC4RF51L, phenylalanine 51 to leucine) (23). The gene discussed is MC4R; the disease is obesity disorder.