The diverse roles of specific GLP-1 receptors in the control of food intake and the response to visceral illness

KP Kinzig, DA D'Alessio, RJ Seeley - Journal of Neuroscience, 2002 - Soc Neuroscience
KP Kinzig, DA D'Alessio, RJ Seeley
Journal of Neuroscience, 2002Soc Neuroscience
Intracerebroventricular administration of glucagon-like peptide-1 (7–36) amide (GLP-1)
reduces food intake and produces symptoms of visceral illness, such as a conditioned taste
aversion (CTA). The central hypothesis of the present work is that separate populations of
GLP-1 receptors mediate the anorexia and taste aversion associated with GLP-1
administration. To test this hypothesis, we first compared the ability of various doses of GLP-
1 to induce anorexia or CTA when administered into either the lateral or fourth ventricle …
Intracerebroventricular administration of glucagon-like peptide-1 (7–36) amide (GLP-1) reduces food intake and produces symptoms of visceral illness, such as a conditioned taste aversion (CTA). The central hypothesis of the present work is that separate populations of GLP-1 receptors mediate the anorexia and taste aversion associated with GLP-1 administration. To test this hypothesis, we first compared the ability of various doses of GLP-1 to induce anorexia or CTA when administered into either the lateral or fourth ventricle. Lateral and fourth ventricular GLP-1 resulted in reduction of food intake at similar doses, whereas only lateral ventricular GLP-1 resulted in a CTA. Such data indicate that both hypothalamic and caudal brainstem GLP-1 receptors are likely to participate in the ability of GLP-1 to reduce food intake. We also hypothesized that the site that must mediate the ability of GLP-1 to induce visceral illness is in the central nucleus of the amygdala (CeA). Administration of 0.2 or 1.0 μg of GLP-1 (7–36) but not the inactive GLP-1 (9–36) resulted in a strong CTA with no accompanying anorexia. In addition, bilateral CeA administration of 2.5 μg of a GLP-1 receptor antagonist before intraperitoneal administration of the toxin lithium chloride resulted in a diminished CTA. Together, these data indicate that separate GLP-1 receptor populations mediate the multiple responses to GLP-1. These results indicate that GLP-1 is a flexible system that can be activated under various circumstances to alter the ingestion of nutrients and/or produce other visceral illness responses, depending on the ascending pathways of the GLP-1 system that are recruited.
Soc Neuroscience