Role of sirtuin 1 in the regulation of hepatic gene expression by thyroid hormone

Shalini Thakran, Pragya Sharma, Ramy R. Attia, Roderick Hori, Xiong Deng, Marshall Elam, Edwards Park

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Sirtuin 1 (SIRT1) is a nuclear deacetylase that modulates lipid metabolism and enhances mitochondrial activity. SIRT1 targets multiple transcription factors and coactivators. Thyroid hormone (T3) stimulates the expression of hepatic genes involved in mitochondrial fatty acid oxidation and gluconeogenesis. We reported that T3 induces genes for carnitine palmitoyltransferase (cpt1a), pyruvate dehydrogenase kinase 4 (pdk4), and phosphoenolpyruvate carboxykinase (pepck). SIRT1 increases the expression of these genes via the activation of several factors, including peroxisome proliferator-activated receptor α, estrogen-related receptor α, and peroxisome proliferator-activated receptor γ coactivator (PGC-1α). Previously, we reported that PGC-1α participates in the T3 induction of cpt1a and pdk4 in the liver. Given the overlapping targets of T3 and SIRT1, we investigated whether SIRT1 participated in the T3 regulation of these genes. Resveratrol is a small phenolic compound whose actions include the activation of SIRT1. Addition of resveratrol increased the T3 induction of the pdk4 and cpt1a genes in hepatocytes. Furthermore, expression of SIRT1 in hepatocytes mimicked resveratrol in the regulation of gene expression by T3. The deacetylase activity of SIRT1 was required and PGC-1α was deacetylated following addition of T3. We found that SIRT1 interacted directly with T3 receptor (TRβ). Knockdown of SIRT1 decreased the T 3 induction of cpt1a and pdk4 and reduced the T3 inhibition of sterol response element binding protein (srebp-1c) both in isolated hepatocytes and in rat liver. Our results indicate that SIRT1 contributes to the T3 regulation of hepatic genes.

Original languageEnglish (US)
Pages (from-to)807-818
Number of pages12
JournalJournal of Biological Chemistry
Volume288
Issue number2
DOIs
StatePublished - Jan 11 2013

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Sirtuin 1
Gene Expression Regulation
Thyroid Hormones
Gene expression
Liver
Genes
Hepatocytes
Peroxisome Proliferator-Activated Receptors
Chemical activation
Carnitine O-Palmitoyltransferase
Thyroid Hormone Receptors
Phosphoenolpyruvate
Gluconeogenesis
Response Elements
Triiodothyronine
Sterols
Lipid Metabolism
Estrogen Receptors
Transcriptional Activation
Rats

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Role of sirtuin 1 in the regulation of hepatic gene expression by thyroid hormone. / Thakran, Shalini; Sharma, Pragya; Attia, Ramy R.; Hori, Roderick; Deng, Xiong; Elam, Marshall; Park, Edwards.

In: Journal of Biological Chemistry, Vol. 288, No. 2, 11.01.2013, p. 807-818.

Research output: Contribution to journalArticle

Thakran, Shalini ; Sharma, Pragya ; Attia, Ramy R. ; Hori, Roderick ; Deng, Xiong ; Elam, Marshall ; Park, Edwards. / Role of sirtuin 1 in the regulation of hepatic gene expression by thyroid hormone. In: Journal of Biological Chemistry. 2013 ; Vol. 288, No. 2. pp. 807-818.
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