BES2003 Oral Communications Brain and Behaviour (8 abstracts)
A role for arcuate cocaine and amphetamine regulated transcript in hyperphagia, thermogenesis and cold adaptation
WM Kong 1 , SS Stanley 1 , JV Gardiner 1 , CR Abbott 1 , KG Murphy 1 , A Seth 1 , I Connley 2 , M Ghatei 1 , D Stephens 3 & SR Bloom 1
1Department of Metabolic Medicine, Hammersmith Campus, Faculty of Medicine, Imperial College of Science Technology and Medicine, London, UK; 2Department of Physiology, St Georges Hospital Medical School, London, UK; 3Department of Mathamatics, South Kensington Campus, Faculty of Physical Sciences, Imperial College of Science Technology and Medicine, London, UK.
The hypothalamic peptide, cocaine and amphetamine regulated transcript (CART) was originally reported to act as an anorexigenic peptide. However, we have recently shown that CART injection into the hypothalamic arcuate nucleus (ARC), acutely stimulates food intake. Here, we characterise the role of arcuate nucleus CART in the long term regulation of food intake and brown adipose tissue (BAT) using i) repeated intra-arcuate injection of CART peptide [CART(55-102)] and ii) polyethylenimine mediated gene transfer to the ARC of a plasmid expressing full length CART (pcDNA-CART). All studies used 8-10 adult male rats. Study 1: Rats received twice daily intra-arcuate injections of 0.2 nanomoles CART (55-102) or saline for seven days. Daytime food intake was 60percent higher in the CART (55-102) group (mean plus/minus SEM: 1.85plus/minus0.4grams [CART] vs 0.38plus/minus0.11grams [saline], P less than 0.005). The thermogenic response to the beta 3 agonist, BRL 35135, was 90percent higher (P<0.05) and BAT UCP-1 mRNA expression was 60percent higher (P less than0.05) in the CART(55-102) group. Study 2: pcDNA-CART was stereotactically injected into the ARC of rats. Food intake was significantly increased during four days ad libitum feeding (135plus/minus3grams [pcDNA-CART] vs 125plus/minus3grams [control plasmid], P less than 0.02) and following 24h food withdrawal in CART over-expressing animals. CART over-expressing animals lost 12percent more weight than controls following a 24h fast (P less than 0.01) and BAT UCP-1 mRNA levels (day 25) were 80percent higher (P less than 0.02). Hypothalamic CART-IR release was 40percent higher in the pcDNA-CART injected animals (P less than 0.01). Study 3: Rats were maintained at 4 degC or 22 degC for 21 days. Levels of CART mRNA in the arcuate nucleus of cold acclimatized animals were double those of the warm maintained animals (P less than 0.05). Taken together these results CART suggest a role for ARC CART in cold adaptation
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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