title: 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.
authors.affiliation: Physiology and Behavior Laboratory, Institute of Food, Nutrition, and Health, Swiss Federal Institute of Technology Zurich (ETH Zurich), 8603 Schwerzenbach, Switzerland.
authors.forename: Mukesh
authors.initials: M
authors.lastname: Punjabi
authors.forename: Myrtha
authors.initials: M
authors.lastname: Arnold
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Rüttimann
authors.forename: Mariana
authors.initials: M
authors.lastname: Graber
authors.forename: Nori
authors.initials: N
authors.lastname: Geary
authors.forename: Gustavo
authors.initials: G
authors.lastname: Pacheco-López
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Langhans
mesh_terms: D000818:Animals; D001067:Appetite Depressants / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D001069:Appetite Regulation / Q000187:drug effects; D019167:Appetite Stimulants / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D001070:Appetitive Behavior / Q000187:drug effects; D031608:Area Postrema / Q000187:drug effects / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects; D002491:Central Nervous System Agents / Q000008:administration & dosage / Q000494:pharmacology; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D000067757:Glucagon-Like Peptide-1 Receptor; D007262:Infusions, Intravenous; D057967:Infusions, Intraventricular; D008297:Male; D009419:Nerve Tissue Proteins / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018027:Receptors, Glucagon / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000378:metabolism; D012249:Rhombencephalon / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D001067:Appetite Depressants; D019167:Appetite Stimulants; D002491:Central Nervous System Agents; C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D018027:Receptors, Glucagon; C055453:glucagon-like peptide 1 (7-36)amide; D052216:Glucagon-Like Peptide 1