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

• Published in: Metabolism, clinical and experimental Vol. 49; no. 6; pp. 709 - 717
• Main Authors: Rodriquez de Fonseca, Fernando, Navarro, Miguel, Alvarez, Elvira, Roncero, Isabel, Chowen, Julie A., Maestre, Olivia, Gómez, Raquel, Muñoz, Raúl M., Eng, John, Blázquez, Enrique
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-06-2000; Elsevier
• Subjects: Amines - blood; Animals; Appetite - drug effects; Biological and medical sciences; Body Weight - drug effects; Brain - metabolism; Diabetes Mellitus - drug therapy; Drinking - drug effects; Eating - drug effects; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptides; In Situ Hybridization; Injections, Intraventricular; Injections, Subcutaneous; Male; Medical sciences; Metabolic diseases; Obesity; Obesity - blood; Obesity - drug therapy; Peptide Fragments - administration & dosage; Peptide Fragments - pharmacology; Peptides - administration & dosage; Peptides - pharmacology; Rats; Rats, Wistar; Rats, Zucker; Receptors, Glucagon - agonists; RNA, Messenger - metabolism; Venoms; Obesity; Agonist; Rat; Treatment efficiency; Rodentia; Nutrition disorder; Weight loss; Non insulin dependent diabetes; Glucagon like peptide 1; Vertebrata; Mammalia; Food intake; Animal; Intracerebral administration; Satiety; Subcutaneous administration; Nutritional status; Biological receptor
• ISSN: 0026-0495; 1532-8600
• DOI: 10.1053/meta.2000.6251

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.