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Prot Cell    2011, Vol. 2 Issue (5) : 358-368    https://doi.org/10.1007/s13238-011-1046-x      PMID: 21614672
REVIEW
Thyroid hormone action in metabolic regulation
Yiyun Song, Xuan Yao, Hao Ying()
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China
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Abstract

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.
Keywords thyroid hormone      thyroid hormone receptor      metabolic regulation      central and peripheral effect      thyroid diseases     
Corresponding Author(s): Ying Hao,Email:yinghao@sibs.ac.cn   
Issue Date: 01 May 2011
 Cite this article:   
Yiyun Song,Xuan Yao,Hao Ying. Thyroid hormone action in metabolic regulation[J]. Prot Cell, 2011, 2(5): 358-368.
 URL:  
https://academic.hep.com.cn/pac/EN/10.1007/s13238-011-1046-x
https://academic.hep.com.cn/pac/EN/Y2011/V2/I5/358
Whole body Insulin sensitivityLiverPeripheral tissues
HyperthyroidismImpaired glucose toleranceIncreased basal hepatic glucose productionReduced peripheral glucose utilization
Hypothyroidism (rodent)Insulin resistanceDecreased hepatic glucose productionDecreased glucose utilization and turnover (muscle and fat)
Resistance to thyroid hormoneReduction of insulin sensitivityImpaired hepatic insulin sensitivity (?)Accumulation of TG and DAG; increased mitochondrial uncoupling and FA oxidation (muscle)
Tab.1  Association of thyroid diseases, metabolic dysfunction and insulin resistance
Fig.1  Possible mechanisms contributing to the beneficial effect of thyroid hormone mimetics.
Low-density lipoprotein (LDL) and high-density lipoprotein (HDL) pathway, as well as liver triglyceride and cholesterol homeostasis, are orchestrated by multiple factors. Thyroid hormone mimetics increase HDL synthesis, HDL reuptake, LDL uptake, the conversion of cholesterol to bile acid, and decrease fatty acid synthesis by mediating the expression of apolipoprotein A1 (APOA1), scavenger receptor B1 (SRB1), LDL receptor (LDLR), cytochrome P450 7A (CYP7A), and sterol response element binding protein (SREBP1) as indicated, respectively.
Fig.1  Possible mechanisms contributing to the beneficial effect of thyroid hormone mimetics.
Low-density lipoprotein (LDL) and high-density lipoprotein (HDL) pathway, as well as liver triglyceride and cholesterol homeostasis, are orchestrated by multiple factors. Thyroid hormone mimetics increase HDL synthesis, HDL reuptake, LDL uptake, the conversion of cholesterol to bile acid, and decrease fatty acid synthesis by mediating the expression of apolipoprotein A1 (APOA1), scavenger receptor B1 (SRB1), LDL receptor (LDLR), cytochrome P450 7A (CYP7A), and sterol response element binding protein (SREBP1) as indicated, respectively.
Fig.2  Schematic representation of the central and peripheral effects of thyroid hormone in metabolic regulation.
Thyroid hormone actions in the hypothalamus (H), brown adipose tissue (B); white adipose tissue (W), liver (L), and mitochondria (M) are summarized.
Fig.2  Schematic representation of the central and peripheral effects of thyroid hormone in metabolic regulation.
Thyroid hormone actions in the hypothalamus (H), brown adipose tissue (B); white adipose tissue (W), liver (L), and mitochondria (M) are summarized.
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[1] Bo Peng,Hui Li,Xuan-Xian Peng. Functional metabolomics: from biomarker discovery to metabolome reprogramming[J]. Protein Cell, 2015, 6(9): 628-637.
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