Leptin, the circulating protein that inhibits food intake and energy expenditure, was thought to function through inhibition of the hypothalamic neuropeptide Y (NPY), a stimulator of food intake. However, mouse mutants lacking NPY are normal, suggesting that alternative neuromodulators of food intake must exist. Recently, melanocortin, a neuropeptide acting on the hypothalamic receptor melanocortin4-R, was discovered in mice, controlling energy regulation. This receptor is antagonized by the "agouti" protein in the mutant obese agouti mouse.