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To investigate the molecular mechanisms underlying alcohol\u2010induced liver steatosis or hepatitis, we used a prediabetic animal model. Otsuka Long\u2010Evans Tokushima Fatty (OLETF) and Long\u2010Evans Tokushima Fatty (LETO) rats were pair\u2010fed with an ethanol\u2010containing liquid diet for 6 weeks. Compared with controls, OLETF and LETO rats displayed more pronounced liver steatosis and higher plasma levels of serum glutamic oxaloacetic transaminase\u00a0(SGOT)\u00a0and\u00a0serum\u00a0glutamate\u00a0pyruvate\u00a0transaminase\u00a0(SPGT), indicating liver injury. Ethanol\u2010fed LETO (Pd\u2010L\u2010E) rats showed mild liver steatosis and no inflammation compared with ethanol\u2010fed OLETF (Pd\u2010O\u2010E) rats. Although precursor and active SREBP\u20101 levels in the liver of ethanol\u2010fed OLETF rats significantly increased compared with control diet\u2010fed OLETF rats (Pd\u2010O\u2010C), those of Pd\u2010L\u2010E rats did not. Bone morphogenetic protein (BMP) and TGF\u2010\u03b21 balance in Pd\u2010O\u2010E rats was significantly altered because BMP signaling was upregulated by inducing BMP2, BMP4, BMP7, BMP9, Smad1, and Smad4, whereas TGF\u2010\u03b21, Smad3, and Erk were downregulated. Activation of TGF\u2010\u03b2\/Smad signaling inhibited BMP2 and BMP9 expression and increased epithelial\u2010mesenchymal transition (EMT) marker levels (Hepcidin, Snail, and Twist) in the liver of LETO rats. Livers of ethanol\u2010fed OLETF rats showed increased levels of vimentin, FSP\u20101, \u03b1\u2010SMA, MMP1, MMP13, and collagen III compared with rats of other groups, whereas EMT marker levels did not change. Thus, BMP exerted anti\u2010 and\/or pro\u2010fibrotic effects in ethanol\u2010fed rats. Therefore, BMP and TGF\u2010\u03b2, two key members of the TGF\u2010\u03b2 superfamily, play important but diverse roles in liver steatosis in young LETO and OLETF rats.<\/jats:p>","DOI":"10.1002\/jcb.30385","type":"journal-article","created":{"date-parts":[[2023,2,15]],"date-time":"2023-02-15T20:23:28Z","timestamp":1676492608000},"page":"459-472","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Alcohol\u2010induced increase in BMP levels promotes fatty liver disease in male prediabetic stage Otsuka Long\u2010Evans Tokushima Fatty rats"],"prefix":"10.1002","volume":"124","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8445-0882","authenticated-orcid":false,"given":"Oak\u2010Kee","family":"Hong","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, College of Medicine The Catholic University of Korea Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eun 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