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A role for arcuate cocaine and amphetamine regulated transcript in hyperphagia, thermogenesis, and cold adaptation
Author(s) -
Kong Wing May,
Stanley Sarah,
Gardiner James,
Abbott Caroline,
Murphy Kevin,
Seth Asha,
Connoley Ian,
Ghatei Mohammed,
Stephens David,
Bloom Stephen
Publication year - 2003
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.02-0805fje
Subject(s) - cart , arcuate nucleus , orexigenic , brown adipose tissue , endocrinology , medicine , thermogenesis , hypothalamus , cocaine and amphetamine regulated transcript , biology , adipose tissue , neuropeptide , neuropeptide y receptor , receptor , mechanical engineering , engineering
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 β3 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 4 o C) 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.