{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T08:14:45Z","timestamp":1791188085317,"version":"4.1.0"},"reference-count":45,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2014,4,21]],"date-time":"2014-04-21T00:00:00Z","timestamp":1398038400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Gastro and Hepatol"],"published-print":{"date-parts":[[2014,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Aims<\/jats:title><jats:p>Hepatic steatosis is a metabolic liver disease with the potential to progress to steatohepatitis, cirrhosis, and hepatocellular carcinoma (<jats:styled-content style=\"fixed-case\">HCC<\/jats:styled-content>). The aim of this study was to investigate the impact of <jats:styled-content style=\"fixed-case\">CCAAT<\/jats:styled-content>\/enhancer\u2010binding protein homologous protein (<jats:styled-content style=\"fixed-case\">CHOP<\/jats:styled-content>) deficiency in the development of steatosis\u2010associated progression of <jats:styled-content style=\"fixed-case\">HCC<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Eight\u2010week\u2010old wild\u2010type (<jats:styled-content style=\"fixed-case\">WT<\/jats:styled-content>) and <jats:styled-content style=\"fixed-case\">CHOP<\/jats:styled-content> knockout (<jats:styled-content style=\"fixed-case\">CHOP<\/jats:styled-content>\u2212\/\u2212) mice were fed a normal or methionine\u2010choline\u2010deficient (<jats:styled-content style=\"fixed-case\">MCD<\/jats:styled-content>) diet. Mice were sacrificed after 3 weeks, and steatosis, inflammation, apoptosis, and liver damage were assessed. We also evaluated fibrosis after 8 weeks of nutrition intervention. To explore the role of <jats:styled-content style=\"fixed-case\">CHOP<\/jats:styled-content> in liver carcinogenesis, 25\u2009mg\/kg of diethylnitrosamine (<jats:styled-content style=\"fixed-case\">DEN<\/jats:styled-content>) was injected intraperitoneally into 2\u2010week\u2010old mice, which were then fed the aforementioned diets from 8 to 24 weeks of age. <jats:styled-content style=\"fixed-case\">CHOP<\/jats:styled-content> expression in <jats:styled-content style=\"fixed-case\">HCC<\/jats:styled-content> patient livers was also evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">CHOP<\/jats:styled-content> deficiency did not affect steatosis but significantly reduced apoptotic cells, inflammation scores, and serum liver enzymes. It also significantly suppressed total serum bilirubin levels, fibrotic area size, and messenger <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> expression of profibrotic cytokines. <jats:styled-content style=\"fixed-case\">DEN<\/jats:styled-content>\u2010initiated carcinogenesis was promoted by the <jats:styled-content style=\"fixed-case\">MCD<\/jats:styled-content> diet, while <jats:styled-content style=\"fixed-case\">CHOP<\/jats:styled-content> deficiency significantly attenuated the total number and maximum diameter of tumors and the <jats:styled-content style=\"fixed-case\">K<\/jats:styled-content>i\u201067 labeling index. In human livers, <jats:styled-content style=\"fixed-case\">CHOP<\/jats:styled-content> expression was enhanced in parallel with non\u2010alcoholic steatohepatitis\u2010to\u2010<jats:styled-content style=\"fixed-case\">HCC<\/jats:styled-content> progression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">CHOP<\/jats:styled-content> deficiency attenuated apoptosis, inflammation, fibrosis, and tumorigenesis under fat\u2010loading conditions, indicating that a therapeutic strategy targeting <jats:styled-content style=\"fixed-case\">CHOP<\/jats:styled-content> might be effective for fat\u2010induced liver injury and protecting against promotion of carcinogenesis in patients with liver steatosis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jgh.12481","type":"journal-article","created":{"date-parts":[[2013,12,12]],"date-time":"2013-12-12T03:51:01Z","timestamp":1386820261000},"page":"1109-1118","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":60,"title":["Attenuation of steatohepatitis, fibrosis, and carcinogenesis in mice fed a methionine\u2010choline deficient diet by CCAAT\/enhancer\u2010binding protein homologous protein deficiency"],"prefix":"10.1111","volume":"29","author":[{"given":"Kan","family":"Toriguchi","sequence":"first","affiliation":[{"name":"Department of Surgery Graduate School of Medicine, Kyoto University  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Etsuro","family":"Hatano","sequence":"additional","affiliation":[{"name":"Department of Surgery Graduate School of Medicine, Kyoto University  Kyoto 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