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Role of SIRT1 in regulation of hepatic gene expression by thyroid hormone
Author(s) -
Thakran Shalini,
Sharma Pragya,
Attia Ramy R,
Hori Rod,
Elam Marshall B,
Cook George A,
Park Edwards A
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.564.7
Subject(s) - pdk4 , sirtuin 1 , thyroid hormone receptor , biology , endocrinology , coactivator , medicine , nuclear receptor , thyroid hormone receptor beta , peroxisome proliferator activated receptor , resveratrol , hormone , transcription factor , gene expression , receptor , biochemistry , hormone receptor , gene , downregulation and upregulation , cancer , breast cancer
Thyroid hormone induces expression of hepatic genes such as pyruvate dehydrogenase kinase 4 (PDK4) and carnitine palmitoyltransferase1a (CPT1a) through the thyroid hormone receptor. Peroxisome proliferator‐activated receptor gamma coactivator 1 (PGC‐1α) enhances the thyroid hormone (T3) induction of these genes. The NAD‐dependent sirtuin 1 (SIRT1) deacetylase plays a critical role in cellular metabolism by deacetylating and activating transcription factors including PGC‐1α. The SIRT1 activator, resveratrol, improves mitochondrial function, increases fatty acid oxidation and decreases lipogenesis. Here, we investigated the role of SIRT1 in the T3 regulation of PDK4 and CPT1a genes. Our data indicate that resveratrol increases expression of PDK4 and CPT1a genes in the liver and enhances the T3 induction of these genes. Resveratrol enhanced the T3 induction through the gene promoters. Overexpression of SIRT1 has similar effects to resveratrol whereas knockdown of SIRT 1 reduces the T3 induction of PDK4 and CPT1a. Moreover, SIRT1 interacts with the thyroid hormone receptor β. Our data indicate that SIRT1 plays an important role in the thyroid hormone induction of hepatic genes such as PDK4 and CPT1a. This work was supported by National Institute of Health and American Heart Association.