Glucagon-like Peptide-2 Acts Partially Through Central GLP-2R and MC4R in Mobilizing Stored Lipids from the Intestine

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Publicado en:Nutrients vol. 17, no. 9 (2025), p. 1416
Autor principal: Mukherjee Kundanika
Otros Autores: Khan Muhammad Saad Abdullah, Howland, John G, Xiao Changting
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MDPI AG
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Acceso en línea:Citation/Abstract
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Resumen: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.
ISSN:2072-6643
DOI:10.3390/nu17091416
Fuente:Health & Medical Collection