{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,5]],"date-time":"2026-07-05T22:50:04Z","timestamp":1783291804694,"version":"3.54.6"},"reference-count":26,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":1584,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2011,5]]},"abstract":"<jats:sec>\n            <jats:title>Abstract<\/jats:title>\n            <jats:p>\n                                 <jats:bold>Chronic alcohol causes hepatic steatosis and liver hypoxia. Hypoxia-regulated hypoxia-inducible factor 1-\u03b1, (HIF-1\u03b1) may regulate liporegulatory genes, but the relationship of HIF-1 to steatosis remains unknown. We investigated HIF-1\u03b1 in alcohol-induced hepatic lipid accumulation. Alcohol administration resulted in steatosis, increased liver triglyceride levels, and increased serum alanine aminotransferase (ALT) levels, suggesting liver injury in wild-type (WT) mice. There was increased hepatic HIF-1\u03b1 messenger RNA (mRNA), protein, and DNA-binding activity in alcohol-fed mice compared with controls. Mice engineered with hepatocyte-specific HIF-1 activation (HIF1dPA) had increased HIF-1\u03b1 mRNA, protein, and DNA-binding activity, and alcohol feeding in HIF1dPA mice increased hepatomegaly and hepatic triglyceride compared with WT mice. In contrast, hepatocyte-specific deletion of HIF-1\u03b1 [HIF-1\u03b1(Hep\u2212\/\u2212)], protected mice from alcohol- and lipopolysaccharide (LPS)-induced liver damage, serum ALT elevation, hepatomegaly, and lipid accumulation. HIF-1\u03b1(Hep\u2212\/\u2212), WT, and HIF1dPA mice had equally suppressed levels of peroxisome proliferator-activated receptor \u03b1 mRNA after chronic ethanol, whereas the HIF target, adipocyte differentiation-related protein, was up-regulated in WT mice but not HIF-1\u03b1(Hep\u2212\/\u2212) ethanol-fed\/LPS-challenged mice. The chemokine monocyte chemoattractant protein-1 (MCP-1) was cooperatively induced by alcohol feeding and LPS in WT but not HIF-1\u03b1(Hep\u2212\/\u2212) mice. Using Huh7 hepatoma cells in vitro, we found that MCP-1 treatment induced lipid accumulation and increased HIF-1\u03b1 protein expression as well as DNA-binding activity. Small interfering RNA inhibition of HIF-1\u03b1 prevented MCP-1\u2013induced lipid accumulation, suggesting a mechanistic role for HIF-1\u03b1 in hepatocyte lipid accumulation.<\/jats:bold>\n                                 <jats:bold>\n                                    Conclusion:\n                                 <\/jats:bold>\n                                 <jats:bold>Alcohol feeding results in lipid accumulation in hepatocytes involving HIF-1\u03b1 activation. The alcohol-induced chemokine MCP-1 triggers lipid accumulation in hepatocytes via HIF-1\u03b1 activation, suggesting a mechanistic link between inflammation and hepatic steatosis in alcoholic liver disease. (Hepatology 2011;)<\/jats:bold>\n                              <\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.24256","type":"journal-article","created":{"date-parts":[[2011,3,3]],"date-time":"2011-03-03T21:08:31Z","timestamp":1299186511000},"page":"1526-1537","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":175,"title":["Hepatocyte-specific hypoxia-inducible factor-1\u03b1 is a determinant of lipid accumulation and liver injury in alcohol-induced steatosis in 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