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Heinrichs SC, Lapsansky J, Behan DP, et al. Corticotropin-releasing factor-binding protein ligand inhibitor blunts excessive weight gain in genetically obese Zucker rats and rats during nicotine withdrawal. Proc Natl Acad Sci U S A. 1996;93(26):15475-80doi: 10.1073/pnas.93.26.15475.
Heinrichs, S. C., Lapsansky, J., Behan, D. P., Chan, R. K., Sawchenko, P. E., Lorang, M., Ling, N., Vale, W. W., & De Souza, E. B. (1996). Corticotropin-releasing factor-binding protein ligand inhibitor blunts excessive weight gain in genetically obese Zucker rats and rats during nicotine withdrawal. Proceedings of the National Academy of Sciences of the United States of America, 93(26), 15475-80. https://doi.org/10.1073/pnas.93.26.15475
Heinrichs, S C, et al. "Corticotropin-releasing factor-binding protein ligand inhibitor blunts excessive weight gain in genetically obese Zucker rats and rats during nicotine withdrawal." Proceedings of the National Academy of Sciences of the United States of America vol. 93,26 (1996): 15475-80. doi: https://doi.org/10.1073/pnas.93.26.15475
Heinrichs SC, Lapsansky J, Behan DP, Chan RK, Sawchenko PE, Lorang M, Ling N, Vale WW, De Souza EB. Corticotropin-releasing factor-binding protein ligand inhibitor blunts excessive weight gain in genetically obese Zucker rats and rats during nicotine withdrawal. Proc Natl Acad Sci U S A. 1996 Dec 24;93(26):15475-80. doi: 10.1073/pnas.93.26.15475. PMID: 8986836; PMCID: PMC26429.
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Atypon Free PMC Article

Proc Natl Acad Sci U S A. 1996 Dec 24;93(26):15475-80. doi: 10.1073/pnas.93.26.15475.

Corticotropin-releasing factor-binding protein ligand inhibitor blunts excessive weight gain in genetically obese Zucker rats and rats during nicotine withdrawal.

Proceedings of the National Academy of Sciences of the United States of America

S C Heinrichs, J Lapsansky, D P Behan, R K Chan, P E Sawchenko, M Lorang, N Ling, W W Vale, E B De Souza

Affiliations

  1. Neurocrine Biosciences, Inc., San Diego, CA 92121, USA.

PMID: 8986836 PMCID: PMC26429 DOI: 10.1073/pnas.93.26.15475
Free PMC Article

Abstract

Elevation of the neuropeptide corticotropin-releasing factor (CRF) in the brain is associated with a reduction of food intake and body weight gain in normal and obese animals. A protein that binds CRF and the related peptide, urocortin, with high affinity, CRF-binding protein (CRF-BP), may play a role in energy homeostasis by inactivating members of this peptide family in ingestive and metabolic regulatory brain regions. Intracerebroventricular administration in rats of the high-affinity CRF-BP ligand inhibitor, rat/human CRF (6-33), which dissociates CRF or urocortin from CRF-BP and increases endogenous brain levels of "free" CRF or urocortin significantly blunted exaggerated weight gain in Zucker obese subjects and in animals withdrawn from chronic nicotine. Chronic administration of CRF suppressed weight gain nonselectively by 60% in both Zucker obese and lean control rats, whereas CRF-BP ligand inhibitor treatment significantly reduced weight gain in obese subjects, without altering weight gain in lean control subjects. Nicotine abstinent subjects, but not nicotine-naive controls, experienced a 35% appetite suppression and a 25% weight gain reduction following acute and chronic administration, respectively, of CRF-BP ligand inhibitor. In marked contrast to the effects of a CRF-receptor agonist, the CRF-BP ligand inhibitor did not stimulate adrenocorticotropic hormone secretion or elevate heart rate and blood pressure. These results provide support for the hypothesis that the CRF-BP may function within the brain to limit selected actions of CRF and/or urocortin. Furthermore, CRF-BP may represent a novel and functionally selective target for the symptomatic treatment of excessive weight gain associated with obesity of multiple etiology.

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