Modulation of urocortin-induced hypophagia and weight loss by corticotropin-releasing factor receptor 1 deficiency in mice

Intracerebroventricular injection of CRF or urocortin (Ucn) reduces appetit e and body weight. CRFR1 and CRFR2, the receptors for CRF and Ucn, are expr essed in neurons associated with appetite-control and metabolism, but their relative contributions in mediating CRF- or Ucn-induced hypophagia and wei ght loss are not known. We used homozygous mice lacking CRFR1 (CRFR1-/-) an d wild-type littermates to determine the role of CRFR1 in mediating the cha nges in food intake and body weight following intracerebroventricular admin istration of Ucn. CRFR1-/- mice, which are glucocorticoid deficient, were g iven corticosterone in their drinking water to induce diurnal variations in circulating corticosterone. A 7-day intracerebroventricular infusion of Uc n transiently suppressed ad libitum food intake equally in CRFR1-/- and wil d-type mice. Body weight reduction during Ucn infusion paralleled food inta ke in wild-type mice, but persisted throughout the infusion in CRFR1-/- mic e. After food-deprivation, acute intracerebroventricular injection of Ucn s uppressed food intake for 1.5 h in wild-type mice. By contrast, CRFR1-/- mi ce did not respond to Ucn 1.5 h after injection. At later time points, Ucn suppressed food intake equally in both genotypes. The distinct time courses of CRF-receptor-induced hypophagia suggest that separate pathways act coop eratively to adjust food intake during challenges to homeostasis.