{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T05:51:58Z","timestamp":1790401918918,"version":"4.1.0"},"reference-count":48,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2021,3,5]],"date-time":"2021-03-05T00:00:00Z","timestamp":1614902400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100012540","name":"Guangdong Province Introduction of Innovative R&D Team","doi-asserted-by":"publisher","award":["2016ZT06Y432"],"award-info":[{"award-number":["2016ZT06Y432"]}],"id":[{"id":"10.13039\/100012540","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2020A1515011302"],"award-info":[{"award-number":["2020A1515011302"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:sec><jats:title>New Findings<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item>\n<jats:p><jats:bold>What is the central question of this study?<\/jats:bold><\/jats:p>\n<jats:p>What is the protective benefit of <jats:italic>n<\/jats:italic>\u22123 polyunsaturated fatty acids (PUFAs) on liver fibrosis and what are the relevant signalling pathways in a transgenic mouse model overexpressing the mfat\u20101 enzyme?<\/jats:p>\n<\/jats:list-item>\n<jats:list-item>\n<jats:p><jats:bold>What is the main finding and its importance?<\/jats:bold><\/jats:p>\n<jats:p><jats:italic>n<\/jats:italic>\u22123 PUFA elevation strongly prevented carbon tetrachloride (CCl<jats:sub>4<\/jats:sub>)\u2010induced hepatic damage and inhibited the activation of hepatic stellate cells. <jats:italic>n<\/jats:italic>\u22123 PUFAs suppressed CCl<jats:sub>4<\/jats:sub>\u2010induced activation of mTOR, elevated Bcl\u20102 expression, and reduced Bax level, suggesting that <jats:italic>n<\/jats:italic>\u22123 PUFAs can render strong protective effects against liver fibrosis and point to the potential of mfat\u20101 gene therapy as a treatment modality.<\/jats:p>\n<\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Liver fibrosis is a reversible wound healing response with excessive accumulation of extracellular matrix proteins. It is a globally prevalent disease with ultimately severe pathological consequences. However, very few current clinical therapeutic options are available. Nutritional addition of <jats:italic>n<\/jats:italic>\u22123 polyunsaturated fatty acids (PUFAs) can delay and lessen the development of liver fibrosis. Herein, this study examined the protective benefit of <jats:italic>n<\/jats:italic>\u22123 PUFAs on liver fibrosis and the relevant signalling pathways using a transgenic mouse model overexpressing the mfat\u20101 enzyme that converts <jats:italic>n<\/jats:italic>\u22126 to <jats:italic>n<\/jats:italic>\u22123 PUFAs. Male C57BL\/6 wild\u2010type and mfat\u20101 transgenic mice were administered carbon tetrachloride (CCl<jats:sub>4<\/jats:sub>) or control corn oil by intraperitoneal injection. Blood alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were subsequently measured. CCl<jats:sub>4<\/jats:sub>\u2010induced hepatic damage and fibrosis were assessed using haematoxylin\u2013eosin and Masson's trichrome staining. Western blot assays were used to detect and quantify fibrosis\u2010related proteins and mechanistic target of rapamycin (mTOR) and B\u2010cell lymphoma 2 (Bcl\u20102)\/Bcl\u20102\u2010associated X protein (Bax) signalling components. The direct effect of docosahexaenoic acid (DHA) on primary hepatic stellate cells (HSCs) was also investigated in a co\u2010culture experiment. <jats:italic>n<\/jats:italic>\u22123 PUFAs, as a result of mfat\u20101 activity, had a strong protective effect on liver fibrosis. The elevation of ALT and AST induced by CCl<jats:sub>4<\/jats:sub> was significantly lessened in the mfat\u20101 mice. Histological determination revealed the protective effects of <jats:italic>n<\/jats:italic>\u22123 PUFAs on liver inflammation and collagen deposition. Co\u2010incubation with DHA reduced the expression of profibrogenic factors in the primary HSCs. Moreover, mfat\u20101 transgenic mice showed significant reduction of proteins that are involved in mTOR and Bcl\u20102\/Bax signalling pathways. Collectively, these results suggest that <jats:italic>n<\/jats:italic>\u22123 PUFA elevation strongly prevents CCl<jats:sub>4<\/jats:sub>\u2010induced hepatic damage by directly inhibiting the activation of HSCs and regulating the basal activity of the mTOR and Bcl\u20102\/Bax signalling pathways. Gene therapy applying mfat\u20101 and elevating <jats:italic>n<\/jats:italic>\u22123 PUFAs represents a promising treatment strategy to prevent liver fibrosis.<\/jats:p><\/jats:sec>","DOI":"10.1113\/ep089328","type":"journal-article","created":{"date-parts":[[2021,2,19]],"date-time":"2021-02-19T11:36:49Z","timestamp":1613734609000},"page":"983-993","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Endogenous production of <i>n<\/i>\u22123 polyunsaturated fatty acids protects mice from carbon tetrachloride\u2010induced liver fibrosis by regulating mTOR and Bcl\u20102\/Bax signalling pathways"],"prefix":"10.1113","volume":"106","author":[{"given":"Changfeng","family":"Shan","sequence":"first","affiliation":[{"name":"The School of Biomedical and Pharmaceutical Sciences Guangdong University of Technology  Guangzhou Guangdong Province People's Republic of 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