Document Detail


Central blockade of melanocortin receptors attenuates the metabolic and locomotor responses to peripheral interleukin-1beta administration.
MedLine Citation:
PMID:  18082228     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Loss of appetite and cachexia is an obstacle in the treatment of chronic infection and cancer. Proinflammatory cytokines released from activated immune cells and acting in the central nervous system (CNS) are prime candidates for mediating these metabolic changes, potentially affecting both energy intake as well as energy expenditure. The effect of intravenous administration of two proinflammatory cytokines, interleukin (IL)-1beta (15 microg/kg) and tumor necrosis factor (TNF)-alpha (10 microg/kg), on food and water intake, locomotor activity, oxygen consumption (VO2), and respiratory exchange ratio (RER) was evaluated. The two cytokines elicited a comparable decrease in food intake and activated similar numbers of cells in the paraventricular nucleus of the hypothalamus (PVH), a region that plays a critical role in the regulation of appetite and metabolism (determined via expression of the immediate early gene, c-fos). However, only IL-1beta reduced locomotion and RER, and increased VO2, while TNF-alpha was without effect. To examine the role of the melanocortins in mediating IL-1beta- induced metabolic changes, animals were pretreated centrally with a melanocortin receptor antagonist, HS014. Pretreatment with HS014 blocked the effect of IL-1beta on food intake and RER at later time points (beyond 8 h post injection), as well as the hypoactivity and increased metabolic rate. Further, HS014 blocked the induction of Fos-ir in the PVH. These data highlight the importance of the melanocortin system, particularly within the PVH, in mediating a broad range of metabolic responses to IL-1beta.
Authors:
Keith W Whitaker; Teresa M Reyes
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2007-11-05
Journal Detail:
Title:  Neuropharmacology     Volume:  54     ISSN:  0028-3908     ISO Abbreviation:  Neuropharmacology     Publication Date:  2008 Mar 
Date Detail:
Created Date:  2008-02-05     Completed Date:  2008-06-12     Revised Date:  2013-06-06    
Medline Journal Info:
Nlm Unique ID:  0236217     Medline TA:  Neuropharmacology     Country:  England    
Other Details:
Languages:  eng     Pagination:  509-20     Citation Subset:  IM    
Affiliation:
Department of Biochemistry, Scripps Florida, Jupiter, FL 33458, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Behavior, Animal / drug effects
Drinking / drug effects
Drug Administration Routes
Drug Interactions
Eating / drug effects
Interleukin-1beta / administration & dosage*
Locomotion / drug effects*,  physiology
Male
Oncogene Proteins v-fos / metabolism
Oxygen Consumption / drug effects*
Peptides, Cyclic / pharmacology
Rats
Rats, Sprague-Dawley
Receptors, Melanocortin / antagonists & inhibitors,  physiology*
Time Factors
Tumor Necrosis Factor-alpha / administration & dosage
Grant Support
ID/Acronym/Agency:
DK064086/DK/NIDDK NIH HHS; K01 DK064086-05/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/HS014 cyclic peptide; 0/Interleukin-1beta; 0/Oncogene Proteins v-fos; 0/Peptides, Cyclic; 0/Receptors, Melanocortin; 0/Tumor Necrosis Factor-alpha
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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