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 appetite and body weight. CRFR1 and CRFR2, the receptors for CRF and Ucn, are expressed in neurons associated with appetite-control and metabolism, but their relative contributions in mediating CRF- or Ucn-induced hypophagia and weight loss are not known. We used homozygous mice lacking CRFR1 (CRFR1-/-) and wild-type littermates to determine the role of CRFR1 in mediating the changes in food intake and body weight following intracerebroventricular administration of Ucn. CRFR1-/- mice, which are glucocorticoid deficient, were given corticosterone in their drinking water to induce diurnal variations in circulating corticosterone. A 7-day intracerebroventricular infusion of Ucn transiently suppressed ad libitum food intake equally in CRFR1-/- and wild-type mice. Body weight reduction during Ucn infusion paralleled food intake in wild-type mice, but persisted throughout the infusion in CRFR1-/- mice. After food-deprivation, acute intracerebroventricular injection of Ucn suppressed food intake for 1.5 h in wild-type mice. By contrast, CRFR1-/- mice 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 cooperatively to adjust food intake during challenges to homeostasis.
The Clayton Foundation Laboratories for Peptide Biology, The Salk Institute, La Jolla, California 92037, USA.
M J
MJ
Bradbury
M I
MI
McBurnie
D A
DA
Denton
K F
KF
Lee
W W
WW
Vale
D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D001066:Appetite / Q000187:drug effects / Q000502:physiology*; D002940:Circadian Rhythm; D003345:Corticosterone / Q000008:administration & dosage / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D004326:Drinking; D004435:Eating / Q000187:drug effects / Q000502:physiology*; D005508:Food Deprivation; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018019:Receptors, Corticotropin-Releasing Hormone / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D054832:Urocortins; D015431:Weight Loss / Q000187:drug effects*
D018019:Receptors, Corticotropin-Releasing Hormone; D054832:Urocortins; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone