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LCAT deficiency causes corneal opacities, normochromic normocytic anemia, and progressive renal disease due to Lp\u2010X deposition in the glomeruli. Recombinant LCAT is being investigated as a potential therapy for this disorder. Several hepatic disorders, namely primary biliary cirrhosis, primary sclerosing cholangitis, cholestatic liver disease, and chronic alcoholism also develop Lp\u2010X, which may contribute to the complications of these disorders. We aimed to test the hypothesis that an increase in plasma LCAT could prevent the formation of Lp\u2010X in other diseases besides FLD. We generated a murine model of intrahepatic cholestasis in LCAT\u2010deficient (KO), wild type (WT), and LCAT\u2010transgenic (Tg) mice by gavaging mice with alpha\u2010naphthylisothiocyanate (ANIT), a drug well known to induce intrahepatic cholestasis. Three days after the treatment, all mice developed hyperbilirubinemia and elevated liver function markers (ALT, AST, Alkaline Phosphatase). The presence of high levels of LCAT in the LCAT\u2010Tg mice, however, prevented the formation of Lp\u2010X and other plasma lipid abnormalities in WT and LCAT\u2010KO mice. In addition, we demonstrated that multiple injections of recombinant human LCAT can prevent significant accumulation of Lp\u2010X after ANIT treatment in WT mice. In summary, LCAT can protect against the formation of Lp\u2010X in a murine model of cholestasis and thus recombinant LCAT could be a potential therapy to prevent the formation of Lp\u2010X in other diseases besides FLD.<\/jats:p>","DOI":"10.1002\/prp2.554","type":"journal-article","created":{"date-parts":[[2019,12,30]],"date-time":"2019-12-30T03:19:11Z","timestamp":1577675951000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["LCAT protects against Lipoprotein\u2010X formation in a murine model of drug\u2010induced intrahepatic cholestasis"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9097-2422","authenticated-orcid":false,"given":"Marcelo J. 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Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sotirios K.","family":"Karathanasis","sequence":"additional","affiliation":[{"name":"Lipoprotein Metabolism Section Translational Vascular Medicine Branch National Heart Lung and Blood Institute National Institutes of Health Bethesda MD USA"},{"name":"Cardiovascular and Metabolic Disease Section MedImmune Gaithersburg MD USA"},{"name":"NeoProgen Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan T.","family":"Remaley","sequence":"additional","affiliation":[{"name":"Lipoprotein Metabolism Section Translational Vascular Medicine Branch National Heart Lung and Blood Institute National Institutes of Health Bethesda MD 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