Selective stimulatory actions of corticotropin-releasing factor ligands oncorrelates of energy balance

Acute administration of corticotropin-releasing factor (CRF) results in ano rexic and sympathomimetic effects that suggest efficacy in chronic models o f energy balance. The present studies employed a broad spectrum energy bala nce indices in lean and genetically obese Zucker rats in order to fully cha racterize the pharmacological efficacy of CRF and a CRF binding protein (CR -F-BP) ligand inhibitor, CR-F(6-33), which is thought to liberate CRF from CRF-BP. Acute administration of CRF(6-33) significantly increased CRF2 rece ptor density by 10% within the ventromedial hypothalamic (VMH) nucleus of Z ucker lean rats and decreased density by 10% in Zucker obese rats. A single infusion of CRF(6-33) increased nonshivering thermogenesis by 25-30% as me asured by proton conductance in brown adipose tissue of both lean and obese rats. Chronic CRF(6-33) infusion suppressed body weight gain and elevated core temperature irrespective of genotype while increasing motor activity i n obese rats without altering heart rate or blood pressure. Taken together, these results document strain-dependent, long-term effects of a CRF-BP lig and inhibitor on a select subset of physiological and behavioral measures o f increased energy expenditure. (C) 2001 Elsevier Science Inc. All rights r eserved.