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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Appetite Depressants / administration & dosage
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Appetite Depressants / adverse effects
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Appetite Depressants / pharmacology
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Appetite Regulation* / drug effects
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Appetite Stimulants / administration & dosage
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Appetite Stimulants / adverse effects
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Appetite Stimulants / pharmacology
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Appetitive Behavior / drug effects
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Area Postrema / drug effects
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Area Postrema / metabolism
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Behavior, Animal / drug effects
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Central Nervous System Agents / administration & dosage
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Central Nervous System Agents / pharmacology
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Glucagon-Like Peptide 1 / administration & dosage
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Glucagon-Like Peptide 1 / adverse effects
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Glucagon-Like Peptide 1 / analogs & derivatives
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Glucagon-Like Peptide 1 / antagonists & inhibitors
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Glucagon-Like Peptide 1 / metabolism*
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Glucagon-Like Peptide 1 / pharmacology
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Glucagon-Like Peptide-1 Receptor
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Infusions, Intravenous
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Infusions, Intraventricular
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Male
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Nerve Tissue Proteins / agonists*
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Nerve Tissue Proteins / antagonists & inhibitors
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Nerve Tissue Proteins / metabolism
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Neurons / drug effects
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Neurons / metabolism*
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Peptide Fragments / administration & dosage
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Peptide Fragments / adverse effects
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Peptide Fragments / pharmacology
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Random Allocation
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Rats
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Rats, Sprague-Dawley
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Receptors, Glucagon / agonists*
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Receptors, Glucagon / antagonists & inhibitors
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Receptors, Glucagon / metabolism
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Rhombencephalon / drug effects
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Rhombencephalon / metabolism*
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Signal Transduction* / drug effects
Substances
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Appetite Depressants
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Appetite Stimulants
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Central Nervous System Agents
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Glp1r protein, rat
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Glucagon-Like Peptide-1 Receptor
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Nerve Tissue Proteins
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Peptide Fragments
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Receptors, Glucagon
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glucagon-like peptide 1 (7-36)amide
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Glucagon-Like Peptide 1