Bile acids regulate the transcription of genes that control cholesterol homeostasis through molecular mechanisms that are poorly understood. Physiological concentrations of free and conjugated chenodeoxycholic acid, lithocholic acid, and deoxycholic acid activated the farnesoid X receptor (FXR; NR1H4), an orphan nuclear receptor. As ligands, these bile acids and their conjugates modulated interaction of FXR with a peptide derived from steroid receptor coactivator 1. These results provide evidence for a nuclear bile acid signaling pathway that may regulate cholesterol homeostasis.
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We thank P. A. Dawson for providing the IBAT expression plasmid pCMV-HISBT, B. W. O'Malley, S. Y. Tsai, M.-Y. Tsai, and M. C. Lewis for critically reading the manuscript. Supported in part by NIH grant RO1 DK53366 to D.D.M. and National Institute of Diabetes and Digestive and Kidney Diseases grant F32 DK09793 to A.M.Z.

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Published In

Volume 284 | Issue 5418
21 May 1999

Submission history

Received: 2 March 1999
Accepted: 28 April 1999
Published in print: 21 May 1999


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Derek J. Parks
Molecular Biochemistry,
Steven G. Blanchard
Molecular Biochemistry,
Randy K. Bledsoe
Gyan Chandra
Molecular Endocrinology,
Thomas G. Consler
Steven A. Kliewer
Molecular Endocrinology,
Julie B. Stimmel
Timothy M. Willson*
Medicinal Chemistry, Glaxo Wellcome Research and Development, Research Triangle Park NC, 27709, USA.
Ann Marie Zavacki
Department of Cell Biology, Baylor College of Medicine, Houston, TX 77030, USA.
David D. Moore
Department of Cell Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Jürgen M. Lehmann
Molecular Endocrinology,


To whom correspondence should be addressed. E-mail: [email protected]

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