Central melanocortin system modulates energy intake and expenditure of obese and lean Zucker rats

Melanocortins play a critical role in appetite and body weight regulation, because manipulations of this pathway can lead to the development of obesit y in several animal models. The purpose of this study was to use a melanoco rtin receptor agonist and antagonist to evaluate the involvement of melanoc ortins in feeding, energy metabolism, and body weight regulation in lean an d obese Zucker rats. Central administration of a melanocortin receptor anta gonist (SHU9119) elevated food intake and body weight of lean Zucker rats b ut had little effect in obese Zucker rats. In contrast, the melanocortin re ceptor agonist MTII reduced food intake in both lean and obese rats but was more potent in the obese Zucker rats. These data indicate the existence of functional melanocortin receptors in both lean and obese Zucker rats but s uggest that obese Zucker rats have reduced endogenous melanocortin tone. In addition to its effects on food intake, MTII infusion elevated oxygen cons umption and decreased respiratory quotient dose dependently during the ligh t cycle. Our data suggest that a melanocortin receptor agonist can induce w eight loss by increasing energy expenditure and promoting body fat utilizat ion in addition to its inhibitory effects on food intake in both obese and lean Zucker rats.