Document Detail

A role for arcuate cocaine and amphetamine-regulated transcript in hyperphagia, thermogenesis, and cold adaptation.
MedLine Citation:
PMID:  12958177     Owner:  NLM     Status:  MEDLINE    
We have recently shown that injection of the hypothalamic peptide cocaine and amphetamine regulated transcript (CART) into discrete hypothalamic nuclei stimulates food intake. This stimulation was particularly marked in the arcuate nucleus. Here we show that twice daily intra-arcuate injection of 0.2 nmole CART peptide for 7 days was associated with a 60% higher daytime food intake, an 85% higher thermogenic response to the beta3 agonist BRL 35135, and a 60% increase in brown adipose tissue UCP-1 mRNA. In a separate study, using stereotactically targeted gene transfer, a CART transgene was delivered by using polyethylenimine to the arcuate nucleus of adult rats. Food intake was increased significantly during ad libitum feeding and following periods of food withdrawal and food restriction in CART over-expressing animals. CART over-expressing animals lost 12% more weight than controls following a 24-h fast. Brown adipose tissue uncoupling protein-1 (UCP-1) mRNA levels (collected Day 25) were 80% higher in CART over-expressing animals. Finally, by using quantitative in situ hybridization, we found that chronic cold exposure (20 days at 4oC) increased arcuate nucleus CART mRNA by 124%. Together with the orexigenic and thermogenic effects of CART, this finding suggests a role for arcuate nucleus CART in cold adaptation.
Wing May Kong; Sarah Stanley; James Gardiner; Caroline Abbott; Kevin Murphy; Asha Seth; Ian Connoley; Mohammed Ghatei; David Stephens; Stephen Bloom
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Publication Detail:
Type:  Journal Article     Date:  2003-07-18
Journal Detail:
Title:  FASEB journal : official publication of the Federation of American Societies for Experimental Biology     Volume:  17     ISSN:  1530-6860     ISO Abbreviation:  FASEB J.     Publication Date:  2003 Sep 
Date Detail:
Created Date:  2003-09-05     Completed Date:  2003-10-08     Revised Date:  2012-02-15    
Medline Journal Info:
Nlm Unique ID:  8804484     Medline TA:  FASEB J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1688-90     Citation Subset:  IM    
Department of Metabolic Medicine, Division of Investigative Sciences, Hammersmith Campus, Faculty of Medicine, Imperial College School of Science, Technology and Medicine, London, UK.
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MeSH Terms
Adaptation, Physiological
Adipose Tissue, Brown / drug effects,  metabolism
Arcuate Nucleus / drug effects,  physiology*
Carrier Proteins / metabolism
Cold Temperature*
Eating / drug effects
Hyperphagia / chemically induced,  etiology*
Hypothalamus / secretion
Ion Channels
Membrane Proteins / metabolism
Mitochondrial Proteins
Models, Neurological
Nerve Tissue Proteins / administration & dosage,  genetics,  pharmacology,  physiology*
RNA, Messenger / biosynthesis
Rats, Wistar
Thyrotropin / blood
Reg. No./Substance:
0/Carrier Proteins; 0/Ion Channels; 0/Membrane Proteins; 0/Mitochondrial Proteins; 0/Nerve Tissue Proteins; 0/RNA, Messenger; 0/cocaine- and amphetamine-regulated transcript protein; 0/mitochondrial uncoupling protein; 9002-71-5/Thyrotropin

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

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