Circulating Glucagon-like Peptide-1 (GLP-1) Inhibits Eating in Male Rats by Acting in the Hindbrain and Without Inducing Avoidance

Abstract

To address the neural mediation of the eating-inhibitory effect of circulating glucagon-like peptide-1 (GLP-1), we investigated the effects of 1) intra-fourth ventricular infusion of the GLP-1 receptor antagonist exendin-9 or 2) area postrema lesion on the eating-inhibitory effect of intrameal hepatic portal vein (HPV) GLP-1 infusion in adult male rats. To evaluate the physiological relevance of the observed effect we examined 3) the influence of GLP-1 on flavor acceptance in a 2-bottle conditioned flavor avoidance test, and 4) measured active GLP-1 in the HPV and vena cava (VC) in relation to a meal and in the VC after HPV GLP-1 infusion. Intrameal HPV GLP-1 infusion (1 nmol/kg body weight-5 min) specifically reduced ongoing meal size by almost 40% (P < .05). Intra-fourth ventricular exendin-9 (10 μg/rat) itself did not affect eating, but attenuated (P < .05) the satiating effect of HPV GLP-1. Area postrema lesion also blocked (P < .05) the eating-inhibitory effect of HPV GLP-1. Pairing consumption of flavored saccharin solutions with HPV GLP-1 infusion did not alter flavor acceptance, indicating that HPV GLP-1 can inhibit eating without inducing malaise. A regular chow meal transiently increased (P < .05) HPV, but not VC, plasma active GLP-1 levels, whereas HPV GLP-1 infusion caused a transient supraphysiological increase (P < .01) in VC GLP-1 concentration 3 minutes after infusion onset. The results implicate hindbrain GLP-1 receptors and the area postrema in the eating-inhibitory effect of circulating GLP-1, but question the physiological relevance of the eating-inhibitory effect of iv infused GLP-1 under our conditions.