Peripheral versus central effects of glucagon-like peptide-1 receptor agonists on satiety and body weight loss in Zucker obese rats

Citation
Fr. De Fonseca et al., Peripheral versus central effects of glucagon-like peptide-1 receptor agonists on satiety and body weight loss in Zucker obese rats, METABOLISM, 49(6), 2000, pp. 709-717
Citations number
45
Categorie Soggetti
Endocrinology, Nutrition & Metabolism
Journal title
METABOLISM-CLINICAL AND EXPERIMENTAL
ISSN journal
00260495 → ACNP
Volume
49
Issue
6
Year of publication
2000
Pages
709 - 717
Database
ISI
SICI code
0026-0495(200006)49:6<709:PVCEOG>2.0.ZU;2-Z
Abstract
The present study explores the potential utility of peripheral versus centr al administration of glucagon-like peptide-1 (GLP-1) receptor agonists in t he regulation of feeding behavior in Wistar and Zucker obese rats. Acute ce ntral (intracerebroventricular [ICV]) and peripheral (subcutaneous [SC]) ad ministration of both GLP-1 (7-36) amide and exendin-4 resulted in a reducti on in food intake for at least 4 hours, exendin-4 being much more potent th an GLP-1 (7-36) amide, especially after peripheral administration. Both Zuc ker obese rats (fa/fa) and their lean littermates (Fa/-) responded to acute central and peripheral administration of exendin-4. Moreover, in situ hybr idization revealed specific labeling for the mRNA for GLP-1 receptors in se veral brain areas of both the obese and lean rats. The presence of this rec eptor was also detected by affinity cross-linking assays. Long-term SC admi nistration of exendin-4 (1 single injection per day, 1 hour prior to the on set of the dark phase of the cycle) decreased daily food intake and practic ally blocked weight gain in obese rats. In contrast to previous studies, th ese findings show that peripheral (SC) administration of both GLP-1 recepto r agonists also induces satiety and weight loss in rats, and suggest the po tential usefulness of exendin-4 as a therapeutic tool for the treatment of diabetes and/or obesity. Copyright (C) 2000 by W.B. Saunders Company.