Integration of NPY, AGRP, and melanocortin signals in the hypothalamic paraventricular nucleus: Evidence of a cellular basis for the adipostat

Energy stores are held relatively constant in many mammals. The circuitry n ecessary for maintaining energy homeostasis should (1) sense the amount of energy stored in adipose tissue, (2) sense and integrate the multiple oppos ing signals regarding nutritional state, and (3) provide output regulating energy intake and expenditure to maintain energy homeostasis. We demonstrat e that individual neurons within the paraventricular nucleus of the hypotha lamus (PVH) are capable of detection and integration of orexigenic (neurope ptide Y [NPY]) and anorexigenic (melanocortin) signals, that NPY and melano cortins are functional antagonists of each other within the PVH in the regu lation of feeding behavior, and that melanocortin administration within the PVH regulates both feeding behavior and energy expenditure. These data pro vide a cellular basis for the adipostat within neurons in the PVH that appe ar to be jointly regulated by NPY- and melanocortin-responsive neurons.