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

Abstract

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.

Role of Sirtuin 1 in the Regulation of Hepatic Gene Expression by Thyroid Hormone

“…It was found that addition of T 3 to human peripheral blood mononuclear cells increased the abundance of SIRT1 after 24 h (41). We tested whether T 3 would increase SIRT1 abundance in the liver since other nuclear factors such as PGC-1␣ and C/EBP␤ are induced by T 3 (7,42). We did not observe any elevation of SIRT1 abundance by T 3 in rat hepatocytes (Fig.…”

“…As these genes are often T 3 targets, we speculated that SIRT1 and T 3 might co-regulate gene expression. We previously reported that PGC-1␣ participates in the T 3 induction of several hepatic genes (6,7). PGC-1␣ is activated by SIRT1 via the deacetylation of multiple lysines suggesting that SIRT1 might enhance the T 3 induction via activation of PGC-1␣ (39).…”

“…Although the TRE is located in the promoter, the first intron is needed for the T 3 induction of cpt1a. PGC-1␣ induces the cpt1a gene through elements in the first intron (7). SIRT1 enhanced the T 3 response of Ϫ4495/ ϩ1240 cpt1a-luciferase (Fig.…”

Upregulation of peroxisome proliferator-activated receptor gamma coactivator gene (PGC1A) during weight loss is related to insulin sensitivity but not to energy expenditure

“…These co-factors may be stimulated (or not) according to specific physiopathological situations and/or the tissues in question. For instance, liver PGC1A enhances the stimulatory action of thyroid hormone on CPT1 [37]. If the same mechanism regulates muscle CPT1, the well documented decrease of thyroid function during active weight loss process [38] could conceivably prevent an increase of CPT1 expression.…”

<small>L</small>-Lysine Attenuates Hepatic Steatosis in Senescence-Accelerated Mouse Prone 8 Mice

“…3B). We quantified the mRNA level of the ␤-oxidation related genes PPAR␣ (23,24), CPT-1a (25,26), and ACO (27) in the liver using qRT-PCR. The mRNA expression level of PPAR␣ in the P group tended to be lower than that of the R group (pϭ0.09 vs. P), showing that dietary supplementation with Lys tended to increase PPAR␣ mRNA levels (Fig.…”