Differential expression of cocaine- and amphetamine-regulated transcript and agouti related-protein in chronically food-restricted sheep

Recently, much attention has focused on the role of the melanocortin system in the regulation of energy homeostasis, especially the satiety effects of the pro-opiomelanocortin (POMC)-derived peptide alpha -melanocyte stimulat ing hormone (alpha -MSH). We have found that POMC mRNA levels are similar i n fat and thin sheep and the current study sought to further characterize t he effects of nutritional status on the melanocortin system. To this end, w e studied the expression of agouti-related peptide (AGRP) (an endogenous an tagonist of alpha -MSH) and cocaine- and amphetamine-regulated transcript ( CART), which is co-localized within POMC cells of the arcuate nucleus (ARC) in rodents. Twelve ovariectomized ewes were randomly divided into two grou ps and fed a maintenance (n=6) or restricted diet (n=6). At the time of exp erimentation, the animals had significantly (P <0.0001) different bodyweigh ts (53.4 +/-2.2 kg, ac. libitum vs. 30.4 +/-1.2 kg, food-restricted), which was largely due to altered body fat deposits. In situ hybridization was us ed to study the expression of POMC, AGRP and CART. The expression of POMC i n the ARC was similar in ad libitum and food-restricted animals but the exp ression of AGRP was profoundly increased in the food-restricted group. The expression of CART was abundant throughout the hypothalamus but was not fou nd in the ARC. In food-restricted animals, the expression of CART was lower in the retrochiasmatic nucleus (P <0.01), paraventricular nucleus (P <0.00 1), the dorsomedial nucleus and the lateral hypothalamic area (P <0.05), bu t was higher (P <0.01) in the posterior hypothalamic area. Thus, long-term chances in nutritional status have profound effects on the expression of AG RP and CART in the hypothalamus. (C) 2001 Elsevier Science B.V. All rights reserved.