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Science 21 May 1999:
Vol. 284. no. 5418, pp. 1362 - 1365
DOI: 10.1126/science.284.5418.1362
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Reports

Identification of a Nuclear Receptor for Bile Acids

Makoto Makishima, 1* Arthur Y. Okamoto, 2* Joyce J. Repa, 1* Hua Tu, 2 R. Marc Learned, 2 Alvin Luk, 2 Mitchell V. Hull, 2 Kevin D. Lustig, 2 David J. Mangelsdorf, 1dagger Bei Shan 2

Bile acids are essential for the solubilization and transport of dietary lipids and are the major products of cholesterol catabolism. Results presented here show that bile acids are physiological ligands for the farnesoid X receptor (FXR), an orphan nuclear receptor. When bound to bile acids, FXR repressed transcription of the gene encoding cholesterol 7alpha -hydroxylase, which is the rate-limiting enzyme in bile acid synthesis, and activated the gene encoding intestinal bile acid-binding protein, which is a candidate bile acid transporter. These results demonstrate a mechanism by which bile acids transcriptionally regulate their biosynthesis and enterohepatic transport.

1 Howard Hughes Medical Institute and Department of Pharmacology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75235-9050, USA.
2 Tularik Incorporated, Two Corporate Drive, South San Francisco, CA 94080, USA.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed. E-mail: davo.mango{at}email.swmed.edu

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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
A role for FXR and human FGF-19 in the repression of paraoxonase-1 gene expression by bile acids.
D. M. Shih, H. R. Kast-Woelbern, J. Wong, Y.-R. Xia, P. A. Edwards, and A. J. Lusis (2006)
J. Lipid Res. 47, 384-392
   Abstract »    Full Text »    PDF »
Bile Acids Decrease Hepatic Paraoxonase 1 Expression and Plasma High-Density Lipoprotein Levels Via FXR-Mediated Signaling of FGFR4.
A. Gutierrez, E. P. Ratliff, A. M. Andres, X. Huang, W. L. McKeehan, and R. A. Davis (2006)
Arterioscler Thromb Vasc Biol 26, 301-306
   Abstract »    Full Text »    PDF »
Gallbladder histopathology during murine gallstone formation: relation to motility and concentrating function.
K. J. van Erpecum, D. Q-H. Wang, A. Moschetta, D. Ferri, M. Svelto, P. Portincasa, J.-J. Hendrickx, M. Schipper, and G. Calamita (2006)
J. Lipid Res. 47, 32-41
   Abstract »    Full Text »    PDF »
The Human Na+-Taurocholate Cotransporting Polypeptide Gene Is Activated by Glucocorticoid Receptor and Peroxisome Proliferator-Activated Receptor-{gamma} Coactivator-1{alpha}, and Suppressed by Bile Acids via a Small Heterodimer Partner-Dependent Mechanism.
J. J. Eloranta, D. Jung, and G. A. Kullak-Ublick (2006)
Mol. Endocrinol. 20, 65-79
   Abstract »    Full Text »    PDF »
FXR regulates organic solute transporters {alpha} and {alpha} in the adrenal gland, kidney, and intestine.
H. Lee, Y. Zhang, F. Y. Lee, S. F. Nelson, F. J. Gonzalez, and P. A. Edwards (2006)
J. Lipid Res. 47, 201-214
   Abstract »    Full Text »    PDF »
Ileal Bile Acid-binding Protein, Functionally Associated with the Farnesoid X Receptor or the Ileal Bile Acid Transporter, Regulates Bile Acid Activity in the Small Intestine.
M. Nakahara, N. Furuya, K. Takagaki, T. Sugaya, K. Hirota, A. Fukamizu, T. Kanda, H. Fujii, and R. Sato (2005)
J. Biol. Chem. 280, 42283-42289
   Abstract »    Full Text »    PDF »
Cross-Talk between Farnesoid-X-Receptor (FXR) and Peroxisome Proliferator-Activated Receptor {gamma} Contributes to the Antifibrotic Activity of FXR Ligands in Rodent Models of Liver Cirrhosis.
S. Fiorucci, G. Rizzo, E. Antonelli, B. Renga, A. Mencarelli, L. Riccardi, A. Morelli, M. Pruzanski, and R. Pellicciari (2005)
J. Pharmacol. Exp. Ther. 315, 58-68
   Abstract »    Full Text »    PDF »
The Farnesoid X Receptor: A Molecular Link Between Bile Acid and Lipid and Glucose Metabolism.
T. Claudel, B. Staels, and F. Kuipers (2005)
Arterioscler Thromb Vasc Biol 25, 2020-2030
   Abstract »    Full Text »    PDF »
Expression of the Pregnane X Receptor in Mice Antagonizes the Cholic Acid-Mediated Changes in Plasma Lipoprotein Profile.
D. Masson, L. Lagrost, A. Athias, P. Gambert, C. Brimer-Cline, L. Lan, J. D. Schuetz, E. G. Schuetz, and M. Assem (2005)
Arterioscler Thromb Vasc Biol 25, 2164-2169
   Abstract »    Full Text »    PDF »
{alpha}-Crystallin Is a Target Gene of the Farnesoid X-activated Receptor in Human Livers.
F. Y. Lee, H. R. Kast-Woelbern, J. Chang, G. Luo, S. A. Jones, M. C. Fishbein, and P. A. Edwards (2005)
J. Biol. Chem. 280, 31792-31800
   Abstract »    Full Text »    PDF »
The Farnesoid X Receptor Modulates Hepatic Carbohydrate Metabolism during the Fasting-Refeeding Transition.
D. Duran-Sandoval, B. Cariou, F. Percevault, N. Hennuyer, A. Grefhorst, T. H. van Dijk, F. J. Gonzalez, J.-C. Fruchart, F. Kuipers, and B. Staels (2005)
J. Biol. Chem. 280, 29971-29979
   Abstract »    Full Text »    PDF »
Retinoid X Receptor Heterodimers in the Metabolic Syndrome.
A. I. Shulman and D. J. Mangelsdorf (2005)
N. Engl. J. Med. 353, 604-615
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A Farnesoid X Receptor-Small Heterodimer Partner Regulatory Cascade Modulates Tissue Metalloproteinase Inhibitor-1 and Matrix Metalloprotease Expression in Hepatic Stellate Cells and Promotes Resolution of Liver Fibrosis.
S. Fiorucci, G. Rizzo, E. Antonelli, B. Renga, A. Mencarelli, L. Riccardi, S. Orlandi, M. Pruzanski, A. Morelli, and R. Pellicciari (2005)
J. Pharmacol. Exp. Ther. 314, 584-595
   Abstract »    Full Text »    PDF »
Bile acid signaling through FXR induces intracellular adhesion molecule-1 expression in mouse liver and human hepatocytes.
P. Qin, L. A. Borges-Marcucci, M. J. Evans, and D. C. Harnish (2005)
Am J Physiol Gastrointest Liver Physiol 289, G267-G273
   Abstract »    Full Text »    PDF »


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