Urocortin, corticotropin releasing factor-2 receptors and energy balance

Although there is considerable information regarding the role of brain CRF in energy balance, relatively little is known about the role of urocortin ( UCN), which is an equally potent anorexic agent. Therefore, the effects of intracerebroventricular (icv) administration of UCN (0.01-1 nmol/day) on fo od intake and body weight were assessed over a period of 13 days and compar ed with data from CRF-infused counterparts. Although both peptides dose dep endently reduced food intake and weight gain, the effects of CRF were much greater in magnitude than those of UCN, particularly on body weight. Pair-f eeding studies suggested that, while the effects of CRF on body weight coul d not be completely explained by appetite suppression, the effects of UCN a ppeared to be due to its initial impact on food intake. CRF increased brown adipose fat pad and adrenal weights, whereas it reduced thymus and spleen weights. CRF also increased serum corticosterone, triglyceride, FFA, and ch olesterol levels, whereas it reduced glucose. UCN did not produce any consi stent changes in any of these indices of sympathetic nervous system activat ion. Concurrent administration of the CRF2-selective antagonist, antisauvag ine-30 (ASV-30) (30 nmol/day) completely reversed or attenuated the effects of UCN and CRF(1 nmol/day) on food intake and body weight. ASV-80 did not significantly attenuate any of the above CRF-induced changes in tissue weig hts or serum chemistry. These data suggest that the central CRF2 receptor m ay primarily mediate the anorexic, but not the metabolic effects of CRF.