{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T08:01:45Z","timestamp":1762761705567,"version":"3.40.5"},"reference-count":41,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,10,5]],"date-time":"2020-10-05T00:00:00Z","timestamp":1601856000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["16K10489","26861059"],"award-info":[{"award-number":["16K10489","26861059"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Gastro and Hepatol"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Aim<\/jats:title><jats:p>The incidence of non\u2010alcoholic steatohepatitis (NASH)\u2010related hepatocellular carcinoma (HCC) is progressively increasing. However, the pathophysiology and etiology of NASH progression to HCC are unknown. We hypothesized that steatosis was the key factor in NASH\u2010related hepatocarcinogenesis and aimed to evaluate the effects of long\u2010term liver X receptor (LXR) agonist stimulation on hepatic steatosis induced by a high\u2010fat diet and oxidative stress.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used an LXR agonist (T0901317) and CCl<jats:sub>4<\/jats:sub> to induce hepatic steatosis and oxidative stress, respectively. C57BL\/6 mice fed with a high\u2010fat diet were treated with either T0901317\u00a0+\u00a0CCl<jats:sub>4<\/jats:sub> (T09\u00a0+\u00a0CCl<jats:sub>4<\/jats:sub> group) or CCl<jats:sub>4<\/jats:sub> alone (CCl<jats:sub>4<\/jats:sub> group). T0901317 (2.5\u00a0mg\/kg) and CCl<jats:sub>4<\/jats:sub> (0.1\u00a0mL\/kg) were intraperitoneally administered twice weekly for 24\u00a0weeks.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The liver\u2010to\u2010body weight ratio was significantly higher in the T09\u00a0+\u00a0CCl<jats:sub>4<\/jats:sub> group than in the CCl<jats:sub>4<\/jats:sub> group. Mice in the T09\u00a0+\u00a0CCl<jats:sub>4<\/jats:sub> group exhibited abnormal lipid metabolism and NASH\u2010like histopathological features. Additionally, all mice in the T09\u00a0+\u00a0CCl<jats:sub>4<\/jats:sub> group developed liver tumors diagnosed as well\u2010differentiated HCC. The genes identified via microarray analysis were related to NASH and HCC development.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>By combining long\u2010term LXR agonist stimulation with oxidative stress and a high\u2010fat diet, we successfully reproduced liver conditions in mice similar to those in humans with NASH and progression to HCC. Our results provide new insight into NASH\u2010related HCC progression and therapy.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jgh.15239","type":"journal-article","created":{"date-parts":[[2020,9,1]],"date-time":"2020-09-01T20:11:17Z","timestamp":1598991077000},"page":"800-810","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Oxidative stress and Liver X Receptor agonist induce hepatocellular carcinoma in Non\u2010alcoholic steatohepatitis model"],"prefix":"10.1111","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1853-7386","authenticated-orcid":false,"given":"Yoshio","family":"Shimizu","sequence":"first","affiliation":[{"name":"Department of Gastrointestinal and Hepato\u2010Biliary\u2010Pancreatic Surgery, Faculty of Medicine University of Tsukuba  Tsukuba 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