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The emerging role of glucagon-like peptide 1 (GLP-1) and its receptor agonists in gastrointestinal diseases has drawn much attention. A mouse model of acute colitis was conducted using a 7-day protocol of dextran sulfate sodium (DSS, 3% w\/v in drinking water) administration. The efficacy of liraglutide (a GLP-1 receptor agonist) in treating DSS-induced colitis and its accompanying Paneth cell metaplasia was examined and correlated to its impact on the levels of colonic autophagy. Liraglutide effectively ameliorated colitis symptoms in mice. Dose-dependent improvements in disease activity index (DAI), colon length, and histopathological scores of inflammation and mucosal damage were evident in the liraglutide-treated groups compared to the DSS group. In addition, liraglutide reduced the expression of lysozyme and suppressed colonic Paneth cell metaplasia induced by DSS. Notably, liraglutide also enhanced levels of colonic autophagy. Direct visualization of autophagosomes and autolysosomes under an electron microscope along with p62 accumulation following co-treatment with chloroquine supports the role of liraglutide as an autophagy enhancer. Liraglutide ameliorated DSS-induced colitis and prevented Paneth cell metaplasia possibly via enhancing colonic autophagy. Our findings strongly signify liraglutide as a therapeutic option for UC.<\/jats:p>","DOI":"10.1007\/s00210-025-04339-w","type":"journal-article","created":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T05:17:15Z","timestamp":1749100635000},"page":"17173-17185","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Repurposing liraglutide to the management of DSS-induced colitis: a potential for promoting autophagy"],"prefix":"10.1007","volume":"398","author":[{"given":"Ahmed Atef","family":"Saadoun","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alia Hamed","family":"Abdelsattar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amro Hatem","family":"Elsaid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eslam Abdelaziz","family":"Abdelaleam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hazem Khaled","family":"Abdelkader","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hend Mohamed","family":"Ibrahim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merna Sabri","family":"Saad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moumen Said","family":"Ellawi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rana Elshahawi","family":"Elsaid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aya","family":"Maghrabia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dina","family":"Ibrahim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nehal M.","family":"Ramadan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,6,5]]},"reference":[{"key":"4339_CR1","doi-asserted-by":"publisher","unstructured":"Abdelbaqi M, Chidlow JH, Matthews KM, Pavlick KP, Barlow SC, Linscott AJ, Grisham MB, Fowler MR, Kevil CG (2006) Regulation of dextran sodium sulfate induced colitis by leukocyte beta 2 integrins. 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