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Effects range from steatosis and mild inflammation with the Lieber\u2013DeCarli liquid diet to severe inflammation, fibrosis, and pyroptosis seen with the Tsukamoto\u2013French intragastric feeding model. Implementation of all of these models is limited by the labor\u2010intensive nature of the protocols and the specialized skills necessary for successful intragastric feeding. We thus sought to develop a new model to reproduce features of alcohol\u2010induced inflammation and fibrosis with minimal operational requirements.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Over a 16\u2010week period, mice were fed <jats:italic>ad libitum<\/jats:italic> with a pelleted high\u2010fat Western diet (WD; 40% calories from fat) and alcohol added to the drinking water. We found the optimal alcohol consumption to be that at which the alcohol concentration was 20% for 4\u00a0days and 10% for 3\u00a0days per week. Control mice received WD pellets with water alone.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Alcohol consumption was 18 to 20\u00a0g\/kg\/day in males and 20 to 22\u00a0g\/kg\/day in females. Mice in the alcohol groups developed elevated serum transaminase levels after 12\u00a0weeks in males and 10\u00a0weeks in females. At 16\u00a0weeks, both males and females developed liver inflammation, steatosis, and pericellular fibrosis. Control mice on WD without alcohol had mild steatosis only. Alcohol\u2010fed mice showed reduced HNF4\u03b1 mRNA and protein expression. HNF4\u03b1 is a master regulator of hepatocyte differentiation, down\u2010regulation of which is a known driver of hepatocellular failure in alcoholic hepatitis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>A simple\u2010to\u2010administer, 16\u2010week WD alcohol model recapitulates the inflammatory, fibrotic, and gene expression aspects of human alcohol\u2010associated steatohepatitis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.14700","type":"journal-article","created":{"date-parts":[[2021,9,15]],"date-time":"2021-09-15T07:53:18Z","timestamp":1631692398000},"page":"1980-1993","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["A Western diet with alcohol in drinking water recapitulates features of alcohol\u2010associated liver disease in mice"],"prefix":"10.1111","volume":"45","author":[{"given":"Michael","family":"Schonfeld","sequence":"first","affiliation":[{"name":"Department of 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