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Glucagon-like Peptide-2 Acts Partially Through Central GLP-2R and MC4R in Mobilizing Stored Lipids from the Intestine
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Glucagon-like Peptide-2 Acts Partially Through Central GLP-2R and MC4R in Mobilizing Stored Lipids from the Intestine
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Journal Article
Glucagon-like Peptide-2 Acts Partially Through Central GLP-2R and MC4R in Mobilizing Stored Lipids from the Intestine
2025
Overview
Background: Glucagon-like peptide-2 (GLP-2) is a gut hormone secreted in response to nutrient intake and regulates lipid metabolism in the gut. The present study aims to elucidate the underlying mechanism of GLP-2 in stimulating gut lipid secretion in the fasted state by testing whether GLP-2 signals through the brain’s GLP-2 receptor and melanocortin 4 receptor (MC4R). Methods: Sprague-Dawley rats were implanted with a mesenteric lymph duct cannula for measuring gut lipid secretion and an intracerebroventricular cannula for infusion of a GLP-2R antagonist (GLP-2(11-33)), an MC4R antagonist (SHU9119), or saline as a control. The rat received a lipid infusion into the small intestine and a peritoneal injection of GLP-2 five hours later. Results: Brain administration of a GLP-2R antagonist or an MC4R antagonist attenuated the stimulatory effects of peripheral GLP-2 on lymph triglyceride output. These effects were associated with differential changes in the expression of key genes in jejunal endothelial cells, smooth muscle cells, and neuronal cells. Conclusions: These results support the involvement of central GLP-2R and MC4R in a neural pathway for GLP-2 to mobilize lipids stored in the gut during the post-absorptive state.
Publisher
MDPI AG,MDPI
Subject
/ Glucagon
/ Glucagon-Like Peptide 2 - metabolism
/ Glucagon-Like Peptide 2 - pharmacology
/ Glucagon-Like Peptide-2 Receptor - antagonists & inhibitors
/ Glucagon-Like Peptide-2 Receptor - metabolism
/ Intestinal Mucosa - metabolism
/ Lipid Metabolism - drug effects
/ Lipids
/ Male
/ Peptides
/ Rats
/ Receptor, Melanocortin, Type 4 - antagonists & inhibitors
/ Receptor, Melanocortin, Type 4 - metabolism
/ Software
/ Surgery
