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One of the most common models used in\n                    <jats:styled-content style=\"fixed-case\">NASH<\/jats:styled-content>\n                    research is a nutritional model where\n                    <jats:styled-content style=\"fixed-case\">NASH<\/jats:styled-content>\n                    is induced by feeding a diet deficient in both methionine and choline. However, the dietary methionine\u2010\/choline\u2010deficient model in mice can cause severe weight loss and liver atrophy, which are not characteristics of\n                    <jats:styled-content style=\"fixed-case\">NASH<\/jats:styled-content>\n                    seen in human patients. Exclusive, long\u2010term feeding with a high\u2010fat diet (\n                    <jats:styled-content style=\"fixed-case\">HFD<\/jats:styled-content>\n                    ) produced fatty liver and obesity in mice, but the\n                    <jats:styled-content style=\"fixed-case\">HFD<\/jats:styled-content>\n                    for several months did not affect fibrosis. We aimed to establish a mouse model of\n                    <jats:styled-content style=\"fixed-case\">NASH<\/jats:styled-content>\n                    with fibrosis by optimizing the methionine content in the\n                    <jats:styled-content style=\"fixed-case\">HFD<\/jats:styled-content>\n                    . Male mice were fed a choline\u2010deficient,\n                    <jats:styled-content style=\"fixed-case\">L<\/jats:styled-content>\n                    \u2010amino acid\u2010defined, high\u2010fat diet (\n                    <jats:styled-content style=\"fixed-case\">CDAHFD<\/jats:styled-content>\n                    ) consisting of 60\u00a0kcal% fat and 0.1% methionine by weight. After 1\u201314\u00a0weeks of being fed\n                    <jats:styled-content style=\"fixed-case\">CDAHFD<\/jats:styled-content>\n                    , the mice were killed.\n                    <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>\n                    57\n                    <jats:styled-content style=\"fixed-case\">BL<\/jats:styled-content>\n                    \/6\n                    <jats:styled-content style=\"fixed-case\">J<\/jats:styled-content>\n                    mice maintained or gained weight when fed\n                    <jats:styled-content style=\"fixed-case\">CDAHFD<\/jats:styled-content>\n                    , while\n                    <jats:styled-content style=\"fixed-case\">A\/J<\/jats:styled-content>\n                    mice showed a steady decline in body weight (of up to 20% of initial weight). In both strains of mice, plasma levels of alanine aminotransferase increased from week 1, when hepatic steatosis was also observed. By week 6,\n                    <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>\n                    57\n                    <jats:styled-content style=\"fixed-case\">BL<\/jats:styled-content>\n                    \/6\n                    <jats:styled-content style=\"fixed-case\">J<\/jats:styled-content>\n                    mice had developed enlarged fatty liver with fibrosis as assessed by\n                    <jats:styled-content style=\"fixed-case\">M<\/jats:styled-content>\n                    asson's trichrome staining and by hydroxyproline assay. Therefore, this improved\n                    <jats:styled-content style=\"fixed-case\">CDAHFD<\/jats:styled-content>\n                    model may be a mouse model of rapidly progressive liver fibrosis and be potentially useful for better understanding human\n                    <jats:styled-content style=\"fixed-case\">NASH<\/jats:styled-content>\n                    disease and in the development of efficient therapies for this condition.\n                  <\/jats:p>","DOI":"10.1111\/iep.12008","type":"journal-article","created":{"date-parts":[[2013,1,11]],"date-time":"2013-01-11T04:01:25Z","timestamp":1357876885000},"page":"93-103","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":519,"title":["An improved mouse model that rapidly develops fibrosis in non\u2010alcoholic steatohepatitis"],"prefix":"10.1111","volume":"94","author":[{"given":"Masahiko","family":"Matsumoto","sequence":"first","affiliation":[{"name":"Fuji\u2010Gotemba Research Laboratories Chugai Research Institute for Medical Science Inc Gotemba Shizuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natsuko","family":"Hada","sequence":"additional","affiliation":[{"name":"Fuji\u2010Gotemba Research Laboratories Chugai Pharmaceutical Co. 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