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Effects of Peripherally Administered Neuromedin U on Energy and Glucose Homeostasis.
MedLine Citation:
PMID:  21586559     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
Authors:
Andrea M Peier; Kunal Desai; James Hubert; Xiaobing Du; Liming Yang; Ying Qian; Jennifer R Kosinski; Joseph M Metzger; Alessandro Pocai; Andrea R Nawrocki; Ronald B Langdon; Donald J Marsh
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-5-17
Journal Detail:
Title:  Endocrinology     Volume:  -     ISSN:  1945-7170     ISO Abbreviation:  -     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-5-18     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0375040     Medline TA:  Endocrinology     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Merck Research Laboratories (A.M.P., K.D., J.H., X.D., L.Y., Y.Q., J.R.K., J.M.M., A.P., A.R.N., R.B.L.), Rahway, New Jersey 07065; and Merck Research Laboratories (D.J.M.), West Point, Pennsylvania 19486.
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