A highly simplified schematic of the central melanocortin system. Receipt of long-term adipostatic signals and acute satiety signals by neurons in arcuate nucleus and brainstem, respectively. Light blue boxes indicate nuclei containing POMC neurons; yellow boxes indicate nuclei containing MC4R neurons that may serve to integrate adipostatic and satiety signals; and pink boxes show some circumventricular organs involved in energy homeostasis. Red arrows designate projections of POMC neurons; blue arrows show projections of agouti-related protein (AgRP neurons). AP, area postrema; ARC, arcuate nucleus; BST, bed nucleus of the stria terminalis; CCK, cholecystokinin; CEA, central nucleus of the amygdala; DMV, dorsal motor nucleus of the vagus; LH, lateral hypothalamic area; LPB, lateral parabrachial nucleus; ME, median eminence; NTS, nucleus tractus solitarius; PVH, paraventricular nucleus of the hypothalamus; RET, reticular formation. For simplicity, only a fraction of the >100 MC4R target sites are shown, and none of the MC3R target nuclei is indicated. Adapted, with permission, from Fan W, Boston BA, Kesterson RA, Hruby VJ & Cone RD (1997) Role of melanocortinergic neurons in feeding and the agouti obesity syndrome. Nature
385 165–168.