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Ethanol feeding induced liver inflammation and neutrophil infiltration that were further increased in FXR KO mice. In addition, collagen accumulation and expression of profibrotic genes were markedly elevated in the liver of alcohol\u2010fed FXR KO compared to wild\u2010type mice, suggesting that ethanol\u2010induced liver fibrosis is enhanced in the absence of FXR. Surprisingly, FXR KO mice showed reduced blood alcohol levels post\u2010binge, while CYP2E1 and ALDH1A1 were upregulated compared to WT mice, suggesting that alcohol metabolism is altered in FXR KO mice. Notably, exacerbated liver injury in FXR KO mice was associated with increased oxidative stress. ALDH1A1 activity was upregulated in FXR\u2010deficient mouse primary hepatocytes, contributing to reactive oxygen species (ROS) generation, in vitro. Finally, using an ALDH1A1 inhibitor, we showed that ALDH1A1 activity is a key contributor to alcohol\u2010induced ROS generation in FXR\u2010deficient hepatocytes, in vitro\n                      <jats:italic>.<\/jats:italic>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>ALD pathogenesis in FXR KO mice correlates with altered ethanol metabolism and increased oxidative stress, providing new insights into the protective function of FXR in ALD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/liv.15374","type":"journal-article","created":{"date-parts":[[2022,7,23]],"date-time":"2022-07-23T02:06:14Z","timestamp":1658541974000},"page":"100-114","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Altered ethanol metabolism and increased oxidative stress enhance alcohol\u2010associated liver injury in farnesoid X receptor\u2010deficient mice"],"prefix":"10.1111","volume":"43","author":[{"given":"Caroline","family":"Morel","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine Beth Israel Deaconess Medical Center and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1277-0128","authenticated-orcid":false,"given":"Vivek","family":"Chowdhary","sequence":"additional","affiliation":[{"name":"Gene Therapy Center University of Massachusetts Medical School  Worcester Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prashanth","family":"Thevkar Nagesh","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine Beth Israel Deaconess Medical Center and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9008-0128","authenticated-orcid":false,"given":"Marcelle","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine Beth Israel Deaconess Medical Center and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle","family":"Hawryluk","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine Beth Israel Deaconess Medical Center and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna","family":"Catalano","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Massachusetts Medical School  Worcester Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciano","family":"Adorini","sequence":"additional","affiliation":[{"name":"Intercept Pharmaceuticals Inc.  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