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Originally published In Press as doi:10.1074/jbc.M212191200 on March 12, 2003

J. Biol. Chem., Vol. 278, Issue 20, 17982-17985, May 16, 2003
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Apolipoprotein A5, a Crucial Determinant of Plasma Triglyceride Levels, Is Highly Responsive to Peroxisome Proliferator-activated Receptor alpha  Activators*

Ngoc Vu-DacDagger §, Philippe GervoisDagger , Heidi JakelDagger , Maxime NowakDagger , Eric BaugéDagger , Hélène DehondtDagger , Bart StaelsDagger , Len A. Pennacchio, Edward M. Rubin, Jamila Fruchart-NajibDagger , and Jean-Charles FruchartDagger

From the Dagger  Département d'Athérosclerose, U.545 INSERM, Institut Pasteur de Lille and Faculté de Pharmacie de Lille, 1 rue Calmette BP 245, 59019 Lille Cédex, France and the  Genome Sciences Department and Joint Genome Institute, Lawrence Berkeley National Laboratory, Berkeley, California 94720

The recently discovered APOA5 gene has been shown in humans and mice to be important in determining plasma triglyceride levels, a major cardiovascular disease risk factor. apoAV represents the first described apolipoprotein where overexpression lowers triglyceride levels. Since fibrates represent a commonly used therapy for lowering plasma triglycerides in humans, we investigated their ability to modulate APOA5 gene expression and consequently influence plasma triglyceride levels. Human primary hepatocytes treated with Wy 14,643 or fenofibrate displayed a strong induction of APOA5 mRNA. Deletion and mutagenesis analyses of the proximal APOA5 promoter firmly demonstrate the presence of a functional peroxisome proliferator-activated receptor response element. These findings demonstrate that APOA5 is a highly responsive peroxisome proliferator-activated receptor alpha  target gene and support its role as a major mediator for how fibrates reduce plasma triglycerides in humans.

* This work was supported by the Leducq 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. Tel.: 33-3-20-87-77-52; Fax: 33-3-20-87-73-60; E-mail: Ngoc.vu-dac@pasteur-lille.fr.

Copyright © 2003 by The American Society for Biochemistry and Molecular Biology, Inc.
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