Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 13 June 2008:
Vol. 320. no. 5882, pp. 1492 - 1496
DOI: 10.1126/science.1158042
Prev | Table of Contents | Next

Reports

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*

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.)

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
The genetics of neutral lipid biosynthesis: an evolutionary perspective.
A. R. Turkish and S. L. Sturley (2009)
Am J Physiol Endocrinol Metab 297, E19-E27
   Abstract »    Full Text »    PDF »
De Novo Ceramide Synthesis Is Required for N-Linked Glycosylation in Plasma Cells.
M. Goldfinger, E. L. Laviad, R. Hadar, M. Shmuel, A. Dagan, H. Park, A. H. Merrill Jr, I. Ringel, A. H. Futerman, and B. Tirosh (2009)
J. Immunol. 182, 7038-7047
   Abstract »    Full Text »    PDF »
Sustained activation of XBP1 splicing leads to endothelial apoptosis and atherosclerosis development in response to disturbed flow.
L. Zeng, A. Zampetaki, A. Margariti, A. E. Pepe, S. Alam, D. Martin, Q. Xiao, W. Wang, Z.-G. Jin, G. Cockerill, et al. (2009)
PNAS 106, 8326-8331
   Abstract »    Full Text »    PDF »
Membrane phospholipid synthesis and endoplasmic reticulum function.
P. Fagone and S. Jackowski (2009)
J. Lipid Res. 50, S311-S316
   Abstract »    Full Text »    PDF »
Thematic Review Series: Glycerolipids. DGAT enzymes and triacylglycerol biosynthesis.
C.-L. E. Yen, S. J. Stone, S. Koliwad, C. Harris, and R. V. Farese Jr. (2008)
J. Lipid Res. 49, 2283-2301
   Abstract »    Full Text »    PDF »
PERK-dependent regulation of lipogenesis during mouse mammary gland development and adipocyte differentiation.
E. Bobrovnikova-Marjon, G. Hatzivassiliou, C. Grigoriadou, M. Romero, D. R. Cavener, C. B. Thompson, and J. A. Diehl (2008)
PNAS 105, 16314-16319
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)