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The physiological processes by which nonobese patients develop NASH and cirrhosis have not yet been determined. Here, we analyzed the effects of dietary methionine content on NASH induced in mice fed on a choline\u2010deficient, methionine\u2010lowered, <jats:sc>l<\/jats:sc>\u2010amino acid\u2010defined high\u2010fat diet (CDAHFD). CDAHFD with insufficient methionine induced insulin sensitivity and enhanced NASH pathology, but without obesity. In contrast, CDAHFD with sufficient methionine induced steatosis, and unlike CDAHFD with insufficient methionine, also induced obesity and insulin resistance. Gene profile analysis revealed that the disease severity in CDAHFD may partially be due to upregulation of the Rho family GTPases pathway and mitochondrial and nuclear receptor signal dysfunction. The signaling factors\/pathways detected in this study may assist in future study of NASH regulation, especially its \u2018nonobese\u2019 subtype.<\/jats:p>","DOI":"10.1002\/2211-5463.13272","type":"journal-article","created":{"date-parts":[[2021,8,14]],"date-time":"2021-08-14T08:18:20Z","timestamp":1628929100000},"page":"2950-2965","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Nonobese mice with nonalcoholic steatohepatitis fed on a choline\u2010deficient, <scp>l<\/scp>\u2010amino acid\u2010defined, high\u2010fat diet exhibit alterations in signaling pathways"],"prefix":"10.1002","volume":"11","author":[{"given":"Noriko","family":"Suzuki\u2010Kemuriyama","sequence":"first","affiliation":[{"name":"Department of Nutritional Science and Food Safety Faculty of Applied Bioscience Tokyo University of Agriculture Setagaya 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