{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T08:42:28Z","timestamp":1783759348138,"version":"3.55.0"},"reference-count":44,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2018,5,20]],"date-time":"2018-05-20T00:00:00Z","timestamp":1526774400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"},{"start":{"date-parts":[[2018,5,20]],"date-time":"2018-05-20T00:00:00Z","timestamp":1526774400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2018,9]]},"abstract":"<jats:p>\n                    Alcohol liver disease (ALD) is one of the major chronic liver diseases worldwide, ranging from fatty liver, alcoholic hepatitis, cirrhosis, and potentially, hepatocellular carcinoma. Epidemiological studies suggest a potential link between ALD and impaired circadian rhythms, but the role of hepatic circadian proteins in the pathogenesis of ALD remains unknown. Here we show that the circadian clock protein BMAL1 in hepatocytes is both necessary and sufficient to protect mice from ALD. Ethanol diet\u2010fed mice with liver\u2010specific knockout (\n                    <jats:italic toggle=\"yes\">Bmal1\u2010LKO<\/jats:italic>\n                    ) or depletion of\n                    <jats:italic toggle=\"yes\">Bmal1<\/jats:italic>\n                    develop more severe liver steatosis and injury as well as a simultaneous suppression of both\n                    <jats:italic toggle=\"yes\">de novo<\/jats:italic>\n                    lipogenesis and fatty acid oxidation, which can be rescued by the supplementation of synthetic PPAR\u03b1 ligands. Restoring\n                    <jats:italic toggle=\"yes\">de novo<\/jats:italic>\n                    lipogenesis in the liver of\n                    <jats:italic toggle=\"yes\">Bmal1\u2010LKO<\/jats:italic>\n                    mice by constitutively active AKT not only elevates hepatic fatty acid oxidation but also alleviates ethanol\u2010induced fatty liver and liver injury. Furthermore, hepatic over\u2010expression of lipogenic transcription factor ChREBP, but not SREBP\u20101c, in the liver of\n                    <jats:italic toggle=\"yes\">Bmal1\u2010LKO<\/jats:italic>\n                    mice also increases fatty acid oxidation and partially reduces ethanol\u2010induced fatty liver and liver injury.\n                    <jats:italic toggle=\"yes\">Conclusion<\/jats:italic>\n                    : we identified a protective role of BMAL1 in hepatocytes against ALD. The protective action of BMAL1 during alcohol consumption depends on its ability to couple ChREBP\u2010induced\n                    <jats:italic toggle=\"yes\">de novo<\/jats:italic>\n                    lipogenesis with PPAR\u03b1\u2010mediated fatty oxidation. (H\n                    <jats:sc>epatology<\/jats:sc>\n                    2018).\n                  <\/jats:p>","DOI":"10.1002\/hep.29878","type":"journal-article","created":{"date-parts":[[2018,3,15]],"date-time":"2018-03-15T07:18:50Z","timestamp":1521098330000},"page":"883-896","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":103,"title":["The hepatic BMAL1\/AKT\/lipogenesis axis protects against alcoholic liver disease in mice via promoting PPAR\u03b1 pathway"],"prefix":"10.1097","volume":"68","author":[{"given":"Deqiang","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Molecular & Integrative Physiology,University of Michigan Medical School,Ann Arbor,MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Tong","sequence":"additional","affiliation":[{"name":"Department of Molecular & Integrative Physiology,University of Michigan Medical School,Ann Arbor,MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley B.","family":"Nelson","sequence":"additional","affiliation":[{"name":"Department of Molecular & Integrative Physiology,University of Michigan Medical School,Ann Arbor,MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ethan","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Molecular & Integrative Physiology,University of Michigan Medical School,Ann Arbor,MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian","family":"Sit","sequence":"additional","affiliation":[{"name":"Department of Molecular & Integrative Physiology,University of Michigan Medical School,Ann Arbor,MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Charney","sequence":"additional","affiliation":[{"name":"Department of Molecular & Integrative Physiology,University of Michigan Medical School,Ann Arbor,MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meichan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Molecular & Integrative Physiology,University of Michigan Medical School,Ann Arbor,MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Bishr","family":"Omary","sequence":"additional","affiliation":[{"name":"Department of Molecular & Integrative Physiology,University of Michigan Medical School,Ann Arbor,MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Molecular & Integrative Physiology,University of Michigan Medical School,Ann Arbor,MI"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2018,5,20]]},"reference":[{"key":"hep29878-bib-0001-20251105","first-page":"193","article-title":"Acute alcohol\u2010induced liver injury","volume":"3","year":"2012","journal-title":"Front Physiol"},{"key":"hep29878-bib-0002-20251105","doi-asserted-by":"crossref","first-page":"6700","DOI":"10.3390\/nu7085304","article-title":"Beverage Consumption: Are Alcoholic and Sugary Drinks Tipping the Balance towards Overweight and 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