Hypothalamic Actions of Neuromedin U

Wren, A. M.; Small, C. J.; Abbott, C. R.; Jethwa, P. H.; Kennedy, A. R.; Murphy, K. G.; Stanley, S. A.; Zollner, A. N.; Ghatei, M. A.; Bloom, S. R.

Abstract

The central nervous system and gut peptide neuromedin U (NMU) inhibits feeding after intracerebroventricular injection. This study explored the hypothalamic actions of NMU on feeding and the hypothalamo-pituitary-adrenal axis. Intraparaventricular nucleus (intra-PVN) NMU dose-dependently inhibited food intake, with a minimum effective dose of 0.1 nmol and a robust effect at 0.3 nmol. Feeding inhibition was mapped by NMU injection into eight hypothalamic areas. NMU (0.3 nmol) inhibited food intake in the PVN (0-1 h, 59 ± 6.9% of the control value; P < 0.001) and arcuate nucleus (0-1 h, 76 ± 10.4% of the control value; P < 0.05). Intra-PVN NMU markedly increased grooming and locomotor behavior and dose-dependently increased plasma ACTH (0.3 nmol NMU, 24.8 ± 1.9 pg/ml; saline, 11.4 ± 1.0; P < 0.001) and corticosterone (0.3 nmol NMU, 275.4 ± 40.5 ng/ml; saline, 129.4 ± 25.0; P < 0.01). Using hypothalamic explants in vitro, NMU stimulated CRH (100 nM NMU, 5.9 ± 0.95 pmol/explant; basal, 3.8 ± 0.39; P < 0.01) and arginine vasopressin release (100 nM NMU, 124.5 ± 21.8 fmol/explant; basal, 74.5 ± 7.6; P < 0.01). Leptin stimulated NMU release (141.9 ± 20.4 fmol/explant; basal, 92.9 ± 9.4; P < 0.01). Thus, we describe a novel role for NMU in the PVN to stimulate the hypothalamo-pituitary-adrenal axis and locomotor and grooming behavior and to inhibit feeding.

Citation

Wren, A. M., Small, C. J., Abbott, C. R., Jethwa, P. H., Kennedy, A. R., Murphy, K. G., …Bloom, S. R. (2002). Hypothalamic Actions of Neuromedin U. Endocrinology, 143(11), 4227-4234. https://doi.org/10.1210/en.2002-220308

• Journal Article Type: Article
• Acceptance Date: Jul 18, 2002
• Online Publication Date: Nov 1, 2002
• Publication Date: Nov 1, 2002
• Deposit Date: Jun 25, 2021
• Journal: Endocrinology
• Print ISSN: 0013-7227
• Electronic ISSN: 1945-7170
• Publisher: Oxford University Press
• Peer Reviewed: Peer Reviewed
• Volume: 143
• Issue: 11
• Pages: 4227-4234
• DOI: https://doi.org/10.1210/en.2002-220308
• Public URL: https://nottingham-repository.worktribe.com/output/3158558
• Publisher URL: https://academic.oup.com/endo/article/143/11/4227/2819783