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

Thakur, Sonu Chand; Sharma, Pragya; Attia, Ramy R.; Hori, Roderick T.; Deng, Xiong; Elam, Marshall B.; Park, Edwards A.

doi:10.1074/jbc.m112.437970

Cited by 68 publications

(61 citation statements)

References 55 publications

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“…In addition, it is also reported that SIRT1/PGC-1α axis regulated glucose and lipid metabolism through a PPARα-independent pathway (Peeters et al 2011, Alberdi et al 2013. Moreover, several lines of evidence have indicated that PGC-1α activated by SIRT1 also modulates the effects of thyroid hormone on lipid and glucose homeostasis (Suh et al 2013, Thakran et al 2013. These findings suggest certain connections between hormonal signaling and SIRT1/PGC-1α axis in the regulation of energy metabolism.…”

Section: Sirtuins (Sirts)mentioning

confidence: 80%

PGC-1α, glucose metabolism and type 2 diabetes mellitus

Deng

Shi

et al. 2016

Journal of Endocrinology

138

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Type 2 diabetes mellitus (T2DM) is a chronic disease characterized by glucose metabolic disturbance. A number of transcription factors and coactivators are involved in this process. Peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) is an important transcription coactivator regulating cellular energy metabolism. Accumulating evidence has indicated that PGC-1α is involved in the regulation of T2DM. Therefore, a better understanding of the roles of PGC-1α may shed light on more efficient therapeutic strategies. Here, we review the most recent progress on PGC-1α and discuss its regulatory network in major glucose metabolic tissues such as the liver, skeletal muscle, pancreas and kidney. The significant associations between PGC-1α polymorphisms and T2DM are also discussed in this review.

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Section: Sirtuins (Sirts)mentioning

confidence: 80%

PGC-1α, glucose metabolism and type 2 diabetes mellitus

Deng

Shi

et al. 2016

Journal of Endocrinology

138

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“…While we have not determined the mechanisms of these effects, we suspect that the latter mechanism is at play at least in regulation of Dio1, which contains bona fide TREs within its proximal promoter (Zhang et al 1998). Perhaps more surprising, however, was that T 3 /FGF21-dependent genes were associated with complement activation and the cell cycle and that many classical T 3 -regulated genes involved in cholesterol metabolism , Lammel Lindemann et al 2014, fatty acid synthesis, b-oxidation, and gluconeogenesis (Singh et al 2013, Suh et al 2013, Thakran et al 2013 did not appear in this list. The significance of the dual T 3 /FGF21 dependency displayed by this gene subset is not clear and requires further investigation.…”

Section: Discussionmentioning

confidence: 99%

Thyroid hormone receptor regulates most genes independently of fibroblast growth factor 21 in liver

Zhang¹,

Sieglaff²,

York³

et al. 2014

Journal of Endocrinology

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Thyroid hormone (TH) acts through specific receptors (TRs), which are conditional transcription factors, to induce fibroblast growth factor 21 (FGF21), a peptide hormone that is usually induced by fasting and that influences lipid and carbohydrate metabolism via local hepatic and systemic endocrine effects. While TH and FGF21 display overlapping actions when administered, including reductions in serum lipids, according to the current models these hormones act independently in vivo. In this study, we examined mechanisms of regulation of FGF21 expression by TH and tested the possibility that FGF21 is required for induction of hepatic TH-responsive genes. We confirm that active TH (triiodothyronine (T 3 )) and the TRb-selective thyromimetic GC1 increase FGF21 transcript and peptide levels in mouse liver and that this effect requires TRb. T 3 also induces FGF21 in cultured hepatocytes and this effect involves direct actions of TRb1, which binds a TRE within intron 2 of FGF21. Gene expression profiles of WTand Fgf21-knockout mice are very similar, indicating that FGF21 is dispensable for the majority of hepatic T 3 gene responses. A small subset of genes displays diminished T 3 response in the absence of FGF21. However, most of these are not obviously directly involved in T 3 -dependent hepatic metabolic processes. Consistent with these results, T 3 -dependent effects on serum cholesterol are maintained in the Fgf21 K/K background and we observe no effect of the Fgf21-knockout background on serum triglycerides and glucose. Our findings indicate that T 3 regulates the genes involved in classical hepatic metabolic responses independently of FGF21.

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“…Recently, Thakran et al (16) showed that SirT1 deacetylation of co-activator PGC1␣ may mediate TH induction of CPT1␣ mRNA in the liver. Our findings provide an even greater understanding of TH-mediated transcription by showing that SirT1 plays a critical role in TH-mediated transcription of gluconeogenic genes in addition to those involved in fatty acid ␤ oxidation; thus, SirT1 may be a central regulator of TH metabolic action in the liver.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, histone deacetylases such as SirT1 (a class III histone deacetylase) or HDAC3 (a class I histone deacetylase) can deacetylate FoxO1 to regulate its transcriptional activity in mammalian cells (14,15). Recently, SirT1 has been shown to modulate TH effects on carnitinepalmitoyl transferase 1␣ (CPT1␣) and pyruvate dehydrogenase kinase 4 (PCK4) in rat primary hepatocytes by deacetylating PGC1␣ (16). However, thus far, no functional interactions among Sirt1, FoxO1, and TRs in TH action have been described.…”

mentioning

confidence: 99%

FoxO1 Deacetylation Regulates Thyroid Hormone-induced Transcription of Key Hepatic Gluconeogenic Genes

Singh

Sinha

Zhou

et al. 2013

Journal of Biological Chemistry

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Background: Thyroid hormone (TH) is known to induce transcription of hepatic gluconeogenic genes. Results: TH stimulates FoxO1 deacetylation to increase PCK1 and G6PC transcription. Conclusion: FoxO1 deacetylation by SirT1 is crucial for TH induction of its target genes, PCK1 and G6PC. Significance: This study demonstrates a novel role of FoxO1 in TH-mediated transcription that may explain some of the pleiotropic actions by TH.

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

Cited by 68 publications

References 55 publications

PGC-1α, glucose metabolism and type 2 diabetes mellitus

PGC-1α, glucose metabolism and type 2 diabetes mellitus

Thyroid hormone receptor regulates most genes independently of fibroblast growth factor 21 in liver

FoxO1 Deacetylation Regulates Thyroid Hormone-induced Transcription of Key Hepatic Gluconeogenic Genes

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