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

Rodriguez R. de Fonseca, M. Navarro, E. Alvarez, I. Roncero, J. A. Chowen, O. Maestre, R. Gomez, R. M. Munoz, J. Eng, E. Blazquez

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146 Scopus citations

Abstract

The present study explores the potential utility of peripheral versus central administration of glucagon-like peptide-1 (GLP-1) receptor agonists in the regulation of feeding behavior in Wistar and Zucker obese rats. Acute central (intracerebroventricular [ICV]) and peripheral (subcutaneous [SC]) administration of both GLP-1 (7-36) amide and exendin-4 resulted in a reduction in food intake for at least 4 hours, exendin-4 being much more potent than GLP-1 (7-36) amide, especially after peripheral administration. Both Zucker obese rats (fa/fa) and their lean littermates (Fa/-) responded to acute central and peripheral administration of exendin-4. Moreover, in situ hybridization revealed specific labeling for the mRNA for GLP-1 receptors in several brain areas of both the obese and lean rats. The presence of this receptor was also detected by affinity cross-linking assays. Long-term SC administration of exendin-4 (1 single injection per day, 1 hour prior to the onset of the dark phase of the cycle) decreased daily food intake and practically blocked weight gain in obese rats. In contrast to previous studies, these findings show that peripheral (SC) administration of both GLP- 1 receptor agonists also induces satiety and weight loss in rats, and suggest the potential usefulness of exendin-4 as a therapeutic tool for the treatment of diabetes and/or obesity.

Original languageEnglish
Pages (from-to)709-717
Number of pages9
JournalMetabolism: Clinical and Experimental
Volume49
Issue number6
DOIs
StatePublished - 2000
Externally publishedYes

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