{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T15:37:58Z","timestamp":1770824278446,"version":"3.50.1"},"reference-count":46,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2016,5,11]],"date-time":"2016-05-11T00:00:00Z","timestamp":1462924800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hepatology Research"],"published-print":{"date-parts":[[2017,1]]},"abstract":"<jats:sec><jats:title><jats:italic>Aim:<\/jats:italic><\/jats:title><jats:p>Experimental models of non\u2010alcoholic steatohepatitis (NASH) are still required for understanding the pathophysiology of this disease. This study aimed to examine whether disease progression is accelerated by combining dyslipidemic genetic modification and dietary challenges and develop NASH\u2010associated hepatic fibrosis, cirrhosis, and carcinoma in a short period.<\/jats:p><\/jats:sec><jats:sec><jats:title><jats:italic>Methods:<\/jats:italic><\/jats:title><jats:p>Low\u2010density lipoprotein receptor knockout mice were fed a modified choline\u2010deficient amino acid\u2010defined diet, including 1 w\/w% cholesterol and 41\u00a0kcal% fat, and was comprehensively profiled over 1\u00a0year.<\/jats:p><\/jats:sec><jats:sec><jats:title><jats:italic>Results:<\/jats:italic><\/jats:title><jats:p>Microvesicular and macrovesicular steatosis in the liver was observed from the first week after starting the modified choline\u2010deficient amino acid\u2010defined diet. Macrovesicular steatosis was exacerbated with time and was observed in almost all hepatocytes at week 8, but slightly decreased at week 16. Infiltration of macrophages and neutrophils, and upregulation of hepatic inflammatory cytokines such as tumor necrosis factor\u2010\u03b1 and interleukin\u20101\u03b2 were also observed from week 1. Plasma hepatic transaminase activities were increased at week 1, reached a peak at week 4, and gradually decreased thereafter. In parallel with increases in hepatic gene expression of collagen\u2010I, the hepatic fibrosis area expanded after week 4 and massively spread all over the liver by week 8. Hepatocellular hyperplasia was observed from week 24. Hepatocellular adenoma and carcinoma were observed from week 31 and 39, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title><jats:italic>Conclusion:<\/jats:italic><\/jats:title><jats:p>These results suggest that, in a rodent NASH model with the combination of genetic modification and dietary challenges, hepatic steatosis, inflammatory cell infiltration and hepatic injury, hepatic fibrosis, hepatocellular hyperplasia, adenoma, and carcinoma can be developed in a relatively short period.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hepr.12709","type":"journal-article","created":{"date-parts":[[2016,3,19]],"date-time":"2016-03-19T10:30:14Z","timestamp":1458383414000},"page":"103-115","source":"Crossref","is-referenced-by-count":9,"title":["Non\u2010alcoholic steatohepatitis\u2010associated hepatic fibrosis and hepatocellular carcinoma in a combined mouse model of genetic modification and dietary 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