HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Xu, G. Articles by Salen, G. Search for Related Content PubMed PubMed Citation Articles by Xu, G. Articles by Salen, G. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol. 43, 45-50, January 2002
Copyright © 2002 by Lipid Research, Inc.

Removal of the bile acid pool upregulates cholesterol 7-hydroxylase by deactivating FXR in rabbits

Correspondence to: Guorong Xu, at GI Lab (15A), VA Medical Center, 385 Tremont Avenue, East Orange, NJ 07018-1095., xugu{at}umdnj.edu (E-mail)

We investigated the role of the orphan nuclear receptor farnesoid X receptor (FXR) in the regulation of cholesterol 7-hydroxylase (CYP7A1), using an in vivo rabbit model, in which the bile acid pool, which includes high affinity ligands for FXR, was eliminated. After 7 days of bile drainage, the enterohepatic bile acid pool, in both New Zealand White and Watanabe heritable hyperlipidemic rabbits, was depleted. CYP7A1 activity and mRNA levels increased while FXR was deactivated as indicated by reduced FXR protein and changes in the expression of target genes that served as surrogate markers of FXR activation in the liver and ileum, respectively. Hepatic bile salt export pump mRNA levels and ileal bile acid-binding protein decreased while sterol 12-hydroxylase and sodium/taurocholate cotransporting polypeptide mRNA levels increased in the liver. In addition, hepatic FXR mRNA levels decreased significantly.

The data, taken together, indicate that FXR was deactivated when the bile acid pool was depleted such that CYP7A1 was upregulated. Further, lack of the high affinity ligand supply was associated with downregulation of hepatic FXR mRNA levels. — Xu, G., L-x. Pan, S. K. Erickson, B. M. Forman, B. L. Shneider, M. Ananthanarayanan, X. Li, S. Shefer, N. Balasubramanian, L. Ma, H. Asaoka, S. R. Lear, L. B. Nguyen, I. Dussault, F. J. Suchy, G. S. Tint, and G. Salen. Removal of the bile acid pool upregulates cholesterol 7-hydroxylase by deactivating FXR in rabbits. J. Lipid Res. 2002. 43: 45–50.

Supplementary key words: bile salt export pump, biosynthesis, farnesoid X receptor, ileal bile acid-binding protein, orphan nuclear receptor

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				W. A. Alrefai, Z. Sarwar, S. Tyagi, S. Saksena, P. K. Dudeja, and R. K. Gill Cholesterol modulates human intestinal sodium-dependent bile acid transporter Am J Physiol Gastrointest Liver Physiol, May 1, 2005; 288(5): G978 - G985. [Abstract] [Full Text] [PDF]

				B. G. Bhat, S. R. Rapp, J. A. Beaudry, N. Napawan, D. N. Butteiger, K. A. Hall, C. L. Null, Y. Luo, and B. T. Keller Inhibition of ileal bile acid transport and reduced atherosclerosis in apoE-/- mice by SC-435 J. Lipid Res., September 1, 2003; 44(9): 1614 - 1621. [Abstract] [Full Text] [PDF]

				G. Xu, L.-x. Pan, H. Li, B. M. Forman, S. K. Erickson, S. Shefer, J. Bollineni, A. K. Batta, J. Christie, T.-h. Wang, et al. Regulation of the Farnesoid X Receptor (FXR) by Bile Acid Flux in Rabbits J. Biol. Chem., December 20, 2002; 277(52): 50491 - 50496. [Abstract] [Full Text] [PDF]