JBC

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1074/jbc.M002782200 on June 23, 2000

J. Biol. Chem., Vol. 275, Issue 37, 28947-28953, September 15, 2000
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
275/37/28947    most recent
M002782200v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hunt, M. C.
Right arrow Articles by Alexson, S. E. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hunt, M. C.
Right arrow Articles by Alexson, S. E. H.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

The Peroxisome Proliferator-activated Receptor alpha  (PPARalpha ) Regulates Bile Acid Biosynthesis*

Mary C. Hunt, Yi-Zeng Yang, Gösta Eggertsen, Claes M. CarneheimDagger , Mats Gåfvels, Curt Einarsson§, and Stefan E. H. Alexson

From the Department of Medical Laboratory Sciences and Technology, Division of Clinical Chemistry, Karolinska Institutet, Huddinge University Hospital, S-141 86 Stockholm, the Dagger  Plasma Products R & D, Pharmacia & Upjohn AB, S-112 87 Stockholm, and the § Department of Medicine, Division of Gastroenterology and Hepatology, Karolinska Institutet, Huddinge University Hospital, S-141 86 Stockholm, Sweden

Fibrates are a group of hypolipidemic agents that efficiently lower serum triglyceride levels by affecting the expression of many genes involved in lipid metabolism. These effects are exerted via the peroxisome proliferator-activated receptor alpha  (PPARalpha ). In addition, fibrates also lower serum cholesterol levels, suggesting a possible link between the PPARalpha and cholesterol metabolism. Bile acid formation represents an important pathway for elimination of cholesterol, and the sterol 12alpha -hydroxylase is a branch-point enzyme in the bile acid biosynthetic pathway, which determines the ratio of cholic acid to chenodeoxycholic acid. Treatment of mice for 1 week with the peroxisome proliferator WY-14,643 or fasting for 24 h both induced the sterol 12alpha -hydroxylase mRNA in liver. Using the PPARalpha knockout mouse model, we show that the induction by both treatments was dependent on the PPARalpha . A reporter plasmid containing a putative peroxisome proliferator-response element (PPRE) identified in the rat sterol 12alpha -hydroxylase promoter region was activated by treatment with WY-14,643 in HepG2 cells, being dependent on co-transfection with a PPARalpha expression plasmid. The rat 12alpha -hydroxylase PPRE bound in vitro translated PPARalpha and retinoid X receptor alpha , albeit weakly, in electrophoretic mobility shift assay. Treatment of wild-type mice with WY-14,643 for 1 week resulted in an increased relative amount of cholic acid, an effect that was abolished in the PPARalpha null mice, verifying the functionality of the PPRE in vivo.

* This work was supported by grants from the Swedish Natural Science Research Foundation, Pharmacia & Upjohn, the Swedish Medical Research Council, and the Swedish Heart and Lung Foundation.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: Dept. of Medical Laboratory Sciences and Technology, Division of Clinical Chemistry, Karolinska Institutet, Huddinge University Hospital, S-141 86 Stockholm, Sweden. Tel.: 46-8-58581274; Fax: 46-8-58581260; E-mail: stefan.alexson@chemlab.hs.sll.se.

Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 J. Nutr.Home page
Y. Li, O. Mezei, and N. F. Shay
Human and Murine Hepatic Sterol-12-{alpha}-Hydroxylase and Other Xenobiotic Metabolism mRNA Are Upregulated by Soy Isoflavones
J. Nutr., July 1, 2007; 137(7): 1705 - 1712.
[Abstract] [Full Text] [PDF]

Home page
 GutHome page
P Hruz, C Zimmermann, H Gutmann, L Degen, U Beuers, L Terracciano, J Drewe, and C Beglinger
Adaptive regulation of the ileal apical sodium dependent bile acid transporter (ASBT) in patients with obstructive cholestasis
Gut, March 1, 2006; 55(3): 395 - 402.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
J. Wang, C. Einarsson, C. Murphy, P. Parini, I. Bjorkhem, M. Gafvels, and G. Eggertsen
Studies on LXR- and FXR-mediated effects on cholesterol homeostasis in normal and cholic acid-depleted mice
J. Lipid Res., February 1, 2006; 47(2): 421 - 430.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
Y. Inoue, A.-M. Yu, S. H. Yim, X. Ma, K. W. Krausz, J. Inoue, C. C. Xiang, M. J. Brownstein, G. Eggertsen, I. Bjorkhem, et al.
Regulation of bile acid biosynthesis by hepatocyte nuclear factor 4{alpha}
J. Lipid Res., January 1, 2006; 47(1): 215 - 227.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
K. Solaas, B. F. Kase, V. Pham, K. Bamberg, M. C. Hunt, and S. E. H. Alexson
Differential regulation of cytosolic and peroxisomal bile acid amidation by PPAR{alpha} activation favors the formation of unconjugated bile acids
J. Lipid Res., June 1, 2004; 45(6): 1051 - 1060.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Clin. Nutr.Home page
P. H Bisschop, R. H. Bandsma, F. Stellaard, A. ter Harmsel, A. J Meijer, H. P Sauerwein, F. Kuipers, and J. A Romijn
Low-fat, high-carbohydrate and high-fat, low-carbohydrate diets decrease primary bile acid synthesis in humans
Am. J. Clinical Nutrition, April 1, 2004; 79(4): 570 - 576.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
G. F. Gbaguidi and L. B. Agellon
The inhibition of the human cholesterol 7{alpha}-hydroxylase gene (CYP7A1) promoter by fibrates in cultured cells is mediated via the liver x receptor {alpha} and peroxisome proliferator-activated receptor {alpha} heterodimer
Nucleic Acids Res., February 11, 2004; 32(3): 1113 - 1121.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
D.-J. Shin, J. A. Campos, G. Gil, and T. F. Osborne
PGC-1{alpha} Activates CYP7A1 and Bile Acid Biosynthesis
J. Biol. Chem., December 12, 2003; 278(50): 50047 - 50052.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
O. Barbier, D. Duran-Sandoval, I. Pineda-Torra, V. Kosykh, J.-C. Fruchart, and B. Staels
Peroxisome Proliferator-activated Receptor {alpha} Induces Hepatic Expression of the Human Bile Acid Glucuronidating UDP-glucuronosyltransferase 2B4 Enzyme
J. Biol. Chem., August 29, 2003; 278(35): 32852 - 32860.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. Hoekstra, J. K. Kruijt, M. Van Eck, and T. J. C. van Berkel
Specific Gene Expression of ATP-binding Cassette Transporters and Nuclear Hormone Receptors in Rat Liver Parenchymal, Endothelial, and Kupffer Cells
J. Biol. Chem., July 3, 2003; 278(28): 25448 - 25453.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
M. Fuchs
Bile Acid Regulation of Hepatic Physiology: III. Regulation of bile acid synthesis: past progress and future challenges
Am J Physiol Gastrointest Liver Physiol, April 1, 2003; 284(4): G551 - G557.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
I. Pineda Torra, T. Claudel, C. Duval, V. Kosykh, J.-C. Fruchart, and B. Staels
Bile Acids Induce the Expression of the Human Peroxisome Proliferator-Activated Receptor {alpha} Gene via Activation of the Farnesoid X Receptor
Mol. Endocrinol., February 1, 2003; 17(2): 259 - 272.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
D. Jung, M. Fried, and G. A. Kullak-Ublick
Human Apical Sodium-dependent Bile Salt Transporter Gene (SLC10A2) Is Regulated by the Peroxisome Proliferator-activated Receptor alpha
J. Biol. Chem., August 16, 2002; 277(34): 30559 - 30566.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
J. Y. L. Chiang
Bile Acid Regulation of Gene Expression: Roles of Nuclear Hormone Receptors
Endocr. Rev., August 1, 2002; 23(4): 443 - 463.
[Abstract] [Full Text] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
O. Barbier, I. P. Torra, Y. Duguay, C. Blanquart, J.-C. Fruchart, C. Glineur, and B. Staels
Pleiotropic Actions of Peroxisome Proliferator-Activated Receptors in Lipid Metabolism and Atherosclerosis
Arterioscler. Thromb. Vasc. Biol., May 1, 2002; 22(5): 717 - 726.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
C. J. Sinal, M. Yoon, and F. J. Gonzalez
Antagonism of the Actions of Peroxisome Proliferator-activated Receptor-alpha by Bile Acids
J. Biol. Chem., December 7, 2001; 276(50): 47154 - 47162.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. Zhang and J. Y. L. Chiang
Transcriptional Regulation of the Human Sterol 12alpha -Hydroxylase Gene (CYP8B1). ROLES OF HEPATOCYTE NUCLEAR FACTOR 4alpha IN MEDIATING BILE ACID REPRESSION
J. Biol. Chem., November 2, 2001; 276(45): 41690 - 41699.
[Abstract] [Full Text] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
S. M. Post, H. Duez, P. P. Gervois, B. Staels, F. Kuipers, and H. M.G. Princen
Fibrates Suppress Bile Acid Synthesis via Peroxisome Proliferator-Activated Receptor-{alpha}-Mediated Downregulation of Cholesterol 7{alpha}-Hydroxylase and Sterol 27-Hydroxylase Expression
Arterioscler. Thromb. Vasc. Biol., November 1, 2001; 21(11): 1840 - 1845.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
T. E. Akiyama, C. J. Nicol, C. Fievet, B. Staels, J. M. Ward, J. Auwerx, S. S. T. Lee, F. J. Gonzalez, and J. M. Peters
Peroxisome Proliferator-activated Receptor-alpha Regulates Lipid Homeostasis, but Is Not Associated with Obesity. STUDIES WITH CONGENIC MOUSE LINES
J. Biol. Chem., October 12, 2001; 276(42): 39088 - 39093.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
A. del Castillo-Olivares and G. Gil
Suppression of sterol 12{alpha}-hydroxylase transcription by the short heterodimer partner: insights into the repression mechanism
Nucleic Acids Res., October 1, 2001; 29(19): 4035 - 4042.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
S. VanPatten, N. Ranginani, S. Shefer, L. B. Nguyen, L. Rossetti, and D. E. Cohen
Impaired biliary lipid secretion in obese Zucker rats: leptin promotes hepatic cholesterol clearance
Am J Physiol Gastrointest Liver Physiol, August 1, 2001; 281(2): G393 - G404.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2000 by the American Society for Biochemistry and Molecular Biology.