Abstract: This paper investigated the associations between central neuromedin U (NMU) receptor 2 (NMU2R) and melanocortin (MC) receptor pathway (MCR3/4) in regulation of food intake and energy homeostasis. NMU, the endogenous ligand of NMU2R in hypothalamus, and SHU9119, a highaffinity antagonist of MCR3/4 pathway, were intracerebraventricularly (ICV) administrated to the fasting and nonfasting rats. The effects of NMU2R on feeding behavior and body weights and their relationships with the role of MCR3/4 signaling were evaluated in the absence or presence of SHU9119 in the rat. The results showed that ICV administration of NMU significantly decreased the food intake as observed at different time points. The anorexigenic effect of NMU was partially inhibited by ICV coadministration of NMU and SHU9119. Furthermore, ICV injection of NMU showed a similar pattern of reduced anorexigenic effect of NMU in SHU9119pretreated rats. These results suggest that functional agonism of NMU2R by NMU in the central nervous system can effectively regulate feeding behavior and energy homeostasis. The central modulation of NMU2R on feeding behavior is associated, at least in part, with melanocortin receptor pathway.

Key words: melanocortin receptor, food intake, intracerebroventricular , neuromedin U, melanocortin receptor, food intake, intracerebroventricular