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J. Biol. Chem., Vol. 279, Issue 52, 53963-53971, December 24, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/52/53963    most recent M406028200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend 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 Zhang, Y. Articles by Park, E. A. Search for Related Content PubMed PubMed Citation Articles by Zhang, Y. Articles by Park, E. A. Social Bookmarking                      What's this?

Peroxisomal Proliferator-activated Receptor- Coactivator-1 (PGC-1) Enhances the Thyroid Hormone Induction of Carnitine Palmitoyltransferase I (CPT-I)^*

Yi Zhang, Ke Ma, Shulan Song, Marshall. B. Elam, George A. Cook, and Edwards A. Park

From the Department of Pharmacology, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee 38163

Carnitine palmitoyltransferase I (CPT-I) catalyzes the rate-controlling step in the pathway of mitochondrial fatty acid oxidation. Thyroid hormone will stimulate the expression of the liver isoform of CPT-I (CPT-I). This induction of CPT-I gene expression requires the thyroid hormone response element in the promoter and sequences within the first intron. The peroxisomal proliferator-activated receptor- coactivator-1 (PGC-1) is a coactivator that promotes mitochondrial biogenesis, mitochondrial fatty acid oxidation, and hepatic gluconeogenesis. In addition, PGC-1 will stimulate the expression of CPT-I in primary rat hepatocytes. Here we report that thyroid hormone will increase PGC-1 mRNA and protein levels in rat hepatocytes. In addition, overexpression of PGC-1 will enhance the thyroid hormone induction of CPT-I indicating that PGC-1 is a coactivator for thyroid hormone. By using chromatin immunoprecipitation assays, we show that PGC-1 is associated with both the thyroid hormone response element in the CPT-I gene promoter and the first intron of the CPT-I gene. Our data demonstrate that PGC-1 participates in the stimulation of CPT-I gene expression by thyroid hormone and suggest that PGC-1 is a coactivator for thyroid hormone.

Received for publication, June 1, 2004 , and in revised form, October 4, 2004.

^* This work was supported by National Institutes of Health Grants DK-059368 (to E. A. P.) and HL-66924 (to G. A. C.) and a Veterans Affairs merit award (to M. B. E.). The costs of publication of this article were defrayed in part by the payment of page charges. This 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 Pharmacology, University of Tennessee, College of Medicine, 874 Union Ave., Memphis, TN 38163. Tel.: 901-448-4779; Fax: 901-448-7206; E-mail: epark{at}utmem.edu.

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