Effects of Peripherally Administered Neuromedin U on Energy and Glucose Homeostasis

• Published in: Endocrinology (Philadelphia) Vol. 152; no. 7; pp. 2644 - 2654
• Main Authors: Peier, Andrea M, Desai, Kunal, Hubert, James, Du, Xiaobing, Yang, Liming, Qian, Ying, Kosinski, Jennifer R, Metzger, Joseph M, Pocai, Alessandro, Nawrocki, Andrea R, Langdon, Ronald B, Marsh, Donald J
• Format: Journal Article
• Language: English
• Published: Chevy Chase, MD Endocrine Society 01.07.2011
• Subjects: Animals; Appetite Regulation; Basal Metabolism; Biological and medical sciences; Body Temperature Regulation; Diabetes Mellitus - drug therapy; Energy Metabolism; Food Preferences; Fundamental and applied biological sciences. Psychology; Glucose Intolerance - prevention & control; Isoenzymes - genetics; Isoenzymes - metabolism; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Mice, Transgenic; Molecular Targeted Therapy; Neuropeptides - administration & dosage; Neuropeptides - physiology; Obesity - drug therapy; Rats; Rats, Sprague-Dawley; Receptors, Neurotransmitter - genetics; Receptors, Neurotransmitter - metabolism; Vertebrates: endocrinology; Weight Loss; neuromedin U; Homeostasis; Glucose
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/en.2010-1463

Neuromedin U (NMU) is a highly conserved peptide reported to modulate energy homeostasis. Pharmacological studies have shown that centrally administered NMU inhibits food intake, reduces body weight, and increases energy expenditure. NMU-deficient mice develop obesity, whereas transgenic mice overexpressing NMU become lean and hypophagic. Two high-affinity NMU receptors, NMUR1 and NMUR2, have been identified. NMUR1 is found primarily in the periphery and NMUR2 primarily in the brain, where it mediates the anorectic effects of centrally administered NMU. Given the broad expression pattern of NMU, we evaluated whether peripheral administration of NMU has effects on energy homeostasis. We observed that acute and chronic peripheral administration of NMU in rodents dose-dependently reduced food intake and body weight and that these effects required NMUR1. The anorectic effects of NMU appeared to be partly mediated by vagal afferents. NMU treatment also increased core body temperature and metabolic rate in mice, suggesting that peripheral NMU modulates energy expenditure. Additionally, peripheral administration of NMU significantly improved glucose excursion. Collectively, these data suggest that NMU functions as a peripheral regulator of energy and glucose homeostasis and the development of NMUR1 agonists may be an effective treatment for diabetes and obesity.