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Science 320 (5882): 1492-1496

Copyright © 2008 by the American Association for the Advancement of Science

Regulation of Hepatic Lipogenesis by the Transcription Factor XBP1

Ann-Hwee Lee,1* Erez F. Scapa,2,3 David E. Cohen,2,3 Laurie H. Glimcher1,2*

Abstract: Dietary carbohydrates regulate hepatic lipogenesis by controlling the expression of critical enzymes in glycolytic and lipogenic pathways. We found that the transcription factor XBP1, a key regulator of the unfolded protein response, is required for the unrelated function of normal fatty acid synthesis in the liver. XBP1 protein expression in mice was elevated after feeding carbohydrates and corresponded with the induction of critical genes involved in fatty acid synthesis. Inducible, selective deletion of XBP1 in the liver resulted in marked hypocholesterolemia and hypotriglyceridemia, secondary to a decreased production of lipids from the liver. This phenotype was not accompanied by hepatic steatosis or compromise in protein secretory function. The identification of XBP1 as a regulator of lipogenesis has important implications for human dyslipidemias.

1 Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
2 Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
3 Division of Gastroenterology, Brigham and Women's Hospital, Boston, MA 02115, USA.

* To whom correspondence should be addressed. E-mail: lglimche{at}hsph.harvard.edu (L.H.G.); ahlee{at}hsph.harvard.edu (A.-H.L.)


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