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 food intake and body weight were assessed over a period of 13 days and compared with data from CRF-infused counterparts. Although both peptides dose dependently reduced food intake and weight gain, the effects of CRF were much greater in magnitude than those of UCN, particularly on body weight. Pair-feeding studies suggested that, while the effects of CRF on body weight could not be completely explained by appetite suppression, the effects of UCN appeared 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 cholesterol levels, whereas it reduced glucose. UCN did not produce any consistent changes in any of these indices of sympathetic nervous system activation. Concurrent administration of the CRF2-selective antagonist, antisauvagine-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 weights or serum chemistry. These data suggest that the central CRF2 receptor may primarily mediate the anorexic, but not the metabolic effects of CRF.