Peroxisomal proliferator-activated receptor-γ coactivator-1α (PGC-1α) enhances the thyroid hormone induction of carnitine palmitoyltransferase I (CPT-Iα)

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