Document Detail


Role of central melanocortins in endotoxin-induced anorexia.
MedLine Citation:
PMID:  10070149     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Inflammation and microbial infection produce symptoms, including fever, anorexia, and hypoactivity, that are thought to be mediated by endogenous proinflammatory cytokines. Melanocortins are known to act centrally to suppress effects on fever and other sequelae of proinflammatory cytokine actions in the central nervous system, but the roles of melanocortins in anorexia and hypoactivity occurring during the acute phase response are unknown. The present study was designed to determine the effects of exogenous and endogenous alpha-melanocyte stimulating hormone (alpha-MSH) on lipopolysaccharide (LPS)-induced anorexia in relation to their effects on fever. Rats were fasted overnight to promote feeding behavior, then injected intraperitoneally with LPS (100 micrograms/kg ip), followed 30 min later by intracerebroventricular injection of either alpha-MSH or the melanocortin receptor subtype 3/subtype 4 (MC3-R/MC4-R) antagonist SHU-9119. Food intake, locomotor activity, and body temperature (Tb) were monitored during the ensuing 24-h period. Each of two intracerebroventricular doses of alpha-MSH (30 and 300 ng) potentiated the suppressive effects of LPS on food intake and locomotion, despite the fact that the higher dose alleviated LPS-induced fever. In control rats that were not treated with LPS, only the higher dose of alpha-MSH significantly inhibited food intake, and Tb and locomotor activity were unaffected. To assess the roles of endogenous central melanocortins, LPS-treated rats received intracerebroventricular SHU-9119 (200 ng). Central MC3-R/MC4-R blockade did not affect Tb or food intake in the absence of LPS treatment, but it reversed the LPS-induced reduction in 24-h food intake and increased LPS-induced fever without altering the LPS-induced suppression of locomotion. Taken together, the results suggest that exogenous and endogenous melanocortins acting centrally exert divergent influences on different aspects of the acute phase response, suppressing LPS-induced fever but contributing to LPS-induced anorexia and hypoactivity.
Authors:
Q H Huang; V J Hruby; J B Tatro
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The American journal of physiology     Volume:  276     ISSN:  0002-9513     ISO Abbreviation:  Am. J. Physiol.     Publication Date:  1999 Mar 
Date Detail:
Created Date:  1999-04-15     Completed Date:  1999-04-15     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0370511     Medline TA:  Am J Physiol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  R864-71     Citation Subset:  IM    
Affiliation:
Division of Endocrinology, Diabetes, Metabolism and Molecular Medicine, Department of Medicine and the Tupper Research Institute, Tufts University School of Medicine and New England Medical Center Hospitals, Boston, Massachusetts 02111, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Anorexia / chemically induced*,  physiopathology*
Body Temperature / drug effects
Brain / metabolism*
Eating / drug effects
Endotoxins*
Injections, Intraventricular
Lipopolysaccharides
Male
Melanocyte-Stimulating Hormones / pharmacology
Motor Activity / drug effects
Rats
Rats, Sprague-Dawley
Receptors, Cell Surface / antagonists & inhibitors
Reference Values
alpha-MSH / physiology*
Grant Support
ID/Acronym/Agency:
DK-17420/DK/NIDDK NIH HHS; MH-44691/MH/NIMH NIH HHS
Chemical
Reg. No./Substance:
0/Endotoxins; 0/Lipopolysaccharides; 0/Receptors, Cell Surface; 168482-23-3/SHU 9119; 581-05-5/alpha-MSH; 9002-79-3/Melanocyte-Stimulating Hormones

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