Affordable Access

A role for arcuate cocaine and amphetamine-regulated transcript in hyperphagia, thermogenesis, and cold adaptation.

Authors
  • Kong, Wing May
  • Stanley, Sarah
  • Gardiner, James
  • Abbott, Caroline
  • Murphy, Kevin
  • Seth, Asha
  • Connoley, Ian
  • Ghatei, Mohammed
  • Stephens, David
  • Bloom, Stephen
Type
Published Article
Journal
The FASEB Journal
Publisher
Federation of American Society for Experimental Biology
Publication Date
Sep 01, 2003
Volume
17
Issue
12
Pages
1688–1690
Identifiers
PMID: 12958177
Source
Medline
License
Unknown

Abstract

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.

Report this publication

Statistics

Seen <100 times