Leptin acts on receptors in the hypothalamus of the brain where it inhibits appetite by (1) counteracting the effects of neuropeptide Y (a potent feeding stimulant secreted by cells in the gut and in the hypothalamus); (2) counteracting the effects of anandamide (another potent feeding stimulant that binds to the same receptors as THC), and (3) promoting the synthesis of a-MSH, an appetite suppressant. Ghrelin is a hormone produced mainly by P/D1 cells lining the fundus of the human stomach and epsilon cells of the pancreas that stimulates hunger. Neuropeptide Y is a natural substance that acts on the brain to stimulate eating.Leptin reduces the output of NPY from the hypothalamus, a major production center. Orexins (hypocretins) are neuropeptides primarily localized in the hypothalamus and are implicated in the regulation of a variety of activities, including feeding behavior and energy balance.