{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T17:04:33Z","timestamp":1781715873971,"version":"3.54.5"},"reference-count":51,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T00:00:00Z","timestamp":1745366400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Saskatchewan Health Research Foundation Establishment Grant"},{"name":"a Canadian Institutes of Health Research Project Grant"},{"name":"Department of Anatomy, Physiology, and Pharmacology Devolved Scholarship"},{"name":"Heart and Stroke Foundation of Canada New Investigator Award"},{"name":"Henry J. M. Barnett Scholarship"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>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\u2019s 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.<\/jats:p>","DOI":"10.3390\/nu17091416","type":"journal-article","created":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T06:38:37Z","timestamp":1745390317000},"page":"1416","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Glucagon-like Peptide-2 Acts Partially Through Central GLP-2R and MC4R in Mobilizing Stored Lipids from the Intestine"],"prefix":"10.3390","volume":"17","author":[{"given":"Kundanika","family":"Mukherjee","sequence":"first","affiliation":[{"name":"Department of Anatomy, Physiology and Pharmacology, College of Medicine, University of Saskatchewan, 107 Wiggins Road, Saskatoon, SK S7N 5E5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Saad Abdullah","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Physiology and Pharmacology, College of Medicine, University of Saskatchewan, 107 Wiggins Road, Saskatoon, SK S7N 5E5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3326-7118","authenticated-orcid":false,"given":"John G.","family":"Howland","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Physiology and Pharmacology, College of Medicine, University of Saskatchewan, 107 Wiggins Road, Saskatoon, SK S7N 5E5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changting","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Physiology and Pharmacology, College of Medicine, University of Saskatchewan, 107 Wiggins Road, Saskatoon, SK S7N 5E5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"997\u20131005.e4","DOI":"10.1053\/j.gastro.2009.05.051","article-title":"Glucagon-Like Peptide-2 Increases Intestinal Lipid Absorption and Chylomicron Production via CD36","volume":"137","author":"Hsieh","year":"2009","journal-title":"Gastroenterology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1053\/j.gastro.2005.10.004","article-title":"Glucagon-Like Peptide 2 Stimulates Glucagon Secretion, Enhances Lipid Absorption, and Inhibits Gastric Acid Secretion in Humans","volume":"130","author":"Meier","year":"2006","journal-title":"Gastroenterology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1161\/ATVBAHA.119.313011","article-title":"Glucose and GLP-2 (Glucagon-Like Peptide-2) Mobilize Intestinal Triglyceride by Distinct Mechanisms","volume":"39","author":"Stahel","year":"2019","journal-title":"Arterioscler. 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