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Am J Physiol Regul Integr Comp Physiol 287: R1190-R1193, 2004. First published July 1, 2004; doi:10.1152/ajpregu.00163.2004
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APPETITE, OBESITY, DIGESTION, AND METABOLISM

Attenuation of lipopolysaccharide anorexia by antagonism of caudal brain stem but not forebrain GLP-1-R

Harvey J. Grill, Jill S. Carmody, L. Amanda Sadacca, Diana L. Williams, and Joel M. Kaplan

Graduate Groups of Psychology and Neuroscience, University of Pennsylvania, Philadelphia, Pennsylvania 19104

Submitted 15 March 2004 ; accepted in final form 22 June 2004

The central glucagon-like peptide-1 (GLP-1) system has been implicated in the control of feeding behavior. Here we explore GLP-1 mediation of the anorexic response to administration of systemic LPS and address the relative importance of caudal brain stem and forebrain GLP-1 receptor (GLP-1-R) for the mediation of the response. Fourth-intracerebroventricular delivery of the GLP-1-R antagonist exendin-(9–39) (10 µg) did not itself affect food intake in the 24 h after injection but significantly attenuated the otherwise robust (~60%) reduction in food intake obtained after LPS (100 µg/kg) treatment. This result highlights a role for caudal brain stem GLP-1-R in the mediation of LPS anorexia but does not rule out the possibility that forebrain receptors also contribute to the response. Forebrain contribution was addressed by delivery of the GLP-1-R antagonist to the third ventricle with the caudal flow of cerebrospinal fluid blocked by occlusion of the cerebral aqueduct. Exendin-(9–39) delivery thus limited to forebrain did not attenuate the anorexic response to LPS. These data suggest that LPS anorexia is mediated, in part, by release of the native peptide acting on GLP-1-R within the caudal brain stem.

feeding behavior; cachexia; neural systems; nucleus of the solitary tract; glucagon-like peptide-1 receptor


Address for reprint requests and other correspondence: H. J. Grill, Graduate Groups of Psychology and Neuroscience, Univ. of Pennsylvania, 3720 Walnut St., Philadelphia, PA 19104 (E-mail: grill{at}psych.upenn.edu)




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