Neuromedin U-induced anorexigenic action is mediated by the corticotropin-releasing hormone receptor-signaling pathway in goldfish

Our recent research has indicated that neuromedin U (NMU) orthologs exist in goldfish, and that NMU consisting of 21 amino acid residues (NMU-21) can potently inhibit food intake in goldfish, as is the case in rodents. However, the anorexigenic pathway of NMU-21 has not yet been clarified in this species. Corticotropin-releasing hormone (CRH), CRH-related peptides and α-melanocyte-stimulating hormone (α-MSH), which exert potent anorexigenic effects, are important mediators involved in feeding regulation in fish. We examined whether CRH or α-MSH mediates NMU-21-induced anorexigenic action in goldfish. We first investigated the effect of intracerebroventricular (ICV) administration of NMU-21 at 100 pmol/g body weight (BW), which is enough to suppress food intake, on expression levels of mRNA for CRH and proopiomelanocortin (POMC) in the hypothalamus. ICV-injected NMU-21 induced a significant increase in the expression level of CRH mRNA, but not that of POMC mRNA. We also examined the effects of ICV administration of the CRH 1/2 receptor antagonist, α-helical CRH(9–41), and the melanocortin 4 receptor antagonist, HS024, on the anorexigenic action of ICV-injected NMU-21. The anorexigenic effect of NMU-21 was blocked by treatment with α-helical CRH(9–41) at 400 pmol/g BW, but not HS024 at 200 pmol/g BW. These results suggest that the anorexigenic action of NMU-21 is mediated by the CRH 1 or 2 receptor-signaling pathway in goldfish.