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A role of hypoxia\u2010inducible factor 1\u03b1 (HIF\u20101\u03b1) in this process has been suggested, but direct evidence is lacking. Here, we used HepG2 cells as a model to study whether HIF\u20101\u03b1 can reduce palmitic acid\u2010induced lipotoxicity and ER stress. In HepG2 cells treated with 500\u2009\u00b5M palmitic acid, HIF\u20101\u03b1 expression increased transiently, the decline was associated with increased cleaved caspase\u20103 expression. Overexpression and knockdown of HIF\u20101\u03b1 decreased and exacerbated, respectively, palmitic acid\u2010induced lipoapoptosis. The overexpression also blunted upregulation of the ER stress markers, C\/EBP homologous protein (CHOP) and chaperone immunoglobulin heavy chain binding protein (Bip), while the knockdown increased the level of CHOP. In line with this, CHOP promoter activity decreased following HIF\u20101\u03b1 binding to the CHOP promoter hypoxia response element. These results indicate that hepatocyte lipotoxicity is associated with decreased HIF\u20101\u03b1 expression. It also suggests that upregulation of HIF\u20101\u03b1 can be a possible strategy to reduce lipotoxicity in non\u2010alcoholic fatty liver disease. J. Cell. Biochem. 115: 1147\u20131158, 2014. \u00a9 2014 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcb.24757","type":"journal-article","created":{"date-parts":[[2014,1,9]],"date-time":"2014-01-09T08:54:23Z","timestamp":1389257663000},"page":"1147-1158","source":"Crossref","is-referenced-by-count":42,"title":["HIF\u20101\u03b1 Expression as a Protective Strategy of HepG2 Cells Against Fatty Acid\u2010Induced Toxicity"],"prefix":"10.1002","volume":"115","author":[{"given":"Wonbaek","family":"Yoo","sequence":"first","affiliation":[{"name":"Division of Endocrinology and Metabolism Department of Internal Medicine Korea University College of Medicine Seoul Republic of Korea"},{"name":"Graduate School of Medicine Korea University Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung Hee","family":"Noh","sequence":"additional","affiliation":[{"name":"Division of Infection and Immunology Graduate School of Medicine Korea University Seoul 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