Thyroid Hormone Regulates Carnitine Palmitoyltransferase Iα Gene Expression through Elements in the Promoter and First Intron

Jansen, Michelle S.; Cook, George A.; Song, Shulan; Park, Edwards A.

doi:10.1074/jbc.m001752200

Cited by 69 publications

(81 citation statements)

References 43 publications

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“…These genes are key regulators of glucose and lipid metabolism. TR has been shown to regulate the transcription of these genes either through TRE or via response elements identified as LXRE or PPRE (Schoonjans et al, 1996;Jansen et al, 2000;Yoshikawa et al, 2001;Araki et al, 2005;Hashimoto et al, 2009;Gauthier et al, 2010). However, most studies were carried out in vitro.…”

Section: Crosstalk With Other Nuclear Receptorsmentioning

confidence: 99%

Thyroid hormone action in metabolic regulation

2011

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Thyroid hormone plays pivotal roles in growth, differentiation, development and metabolic homeostasis via thyroid hormone receptors (TRs) by controlling the expression of TR target genes. The transcriptional activity of TRs is modulated by multiple factors including various TR isoforms, diverse thyroid hormone response elements, different heterodimeric partners, coregulators, and the cellular location of TRs. In the present review, we summarize recent advance in understanding the molecular mechanisms of thyroid hormone action obtained from human subject research, thyroid hormone mimetics application, TR isoform-specific knock-in mouse models, and mitochondrion study with highlights in metabolic regulations. Finally, as future perspectives, we share our thoughts about current challenges and possible approaches to promote our knowledge of thyroid hormone action in metabolism.

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Section: Crosstalk With Other Nuclear Receptorsmentioning

confidence: 99%

Thyroid hormone action in metabolic regulation

2011

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“…Vectors-CPT-I␣-luciferase constructs (CPT-I␣-luc) were transiently transfected into HepG2 cells by the calcium phosphate method (10). Transfections included 2 g of CPT-I␣-luciferase along with RSV-thyroid hormone receptor ␤ (RSV-TR␤) and TK-Renilla vectors.…”

Section: Transient Transfection Of Luciferasementioning

confidence: 99%

“…Construction of the CPT-I␣-luciferase vectors was described previously (10). The Gal4-PGC-1␣ expression vectors were created by generating fragments of the PGC-1␣ cDNA by PCR amplification.…”

Section: Transient Transfection Of Luciferasementioning

confidence: 99%

“…Our laboratory has cloned the promoter for the rat CPT-I␣ gene and identified a thyroid hormone response element (TRE) in the CPT-I␣ promoter at nucleotides Ϫ2938/-2923 (9 -11). We have shown that the CPT-I␣-TRE binds the thyroid hormone receptor (TR) as a heterodimer with the retinoid X receptor (10). There are several unusual features of the induction of CPT-I␣ by T3.…”

mentioning

confidence: 99%

“…First, whereas CPT-I␣ is strongly induced by T3 in the liver, CPT-I␣ is not induced by T3 in the heart (5,12). In addition, sequences within the first intron contribute to the high expression of CPT-I␣ in the liver and are necessary for the full induction of the CPT-I␣ gene by T3 (10,12).…”

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confidence: 99%

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

Zhang

Song

et al. 2004

Journal of Biological Chemistry

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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.

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Insulin Regulation of Ketone Body Metabolism

Ciaraldi

Henry

2004

International Textbook of Diabetes Mellitus

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The overarching concern in the hormonal control of ketone body metabolism is the insulin level. In circumstances where insulin levels are relatively high, such as the fed state, both substrate (free fatty acid, [FFA]) availability and FFA oxidation are suppressed, directing FFA to storage and employing glucose to meet the energy needs of the body. In situations of relative insulin deficiency, such as starvation or type I diabetes, FFA oxidation is increased, driving the production of alternative energy‐producing substrates, ketone bodies, for use by the brain, as well as peripheral tissues. Insulin influences the activity of three key processes: FFA availability (lipolysis), ketone body production (ketogenesis), and disposal in peripheral tissues. All of these processes can be altered in pathophysiologic conditions such as type 1 and type 2 diabetes, obesity, starvation, and hyperthyroidism. The key control point is carnitine palmitoyltransferase‐I (CPT‐I), which mediates the passage of long chain fatty acyl coenzyme A (FA‐CoA) esters across the outer mitochondrial membrane, prior to oxidation or ketogenesis. Insulin regulates CPT‐I both at the level of gene transcription and by influencing the affinity for allosteric modulators. Regulation of hepatic CPT‐I expression or activity holds potential significance as an approach for controlling hyperglycemia and insulin resistance.

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Thyroid Hormone Regulates Carnitine Palmitoyltransferase Iα Gene Expression through Elements in the Promoter and First Intron

Cited by 69 publications

References 43 publications

Thyroid hormone action in metabolic regulation

Thyroid hormone action in metabolic regulation

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

Insulin Regulation of Ketone Body Metabolism

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