Thyroid hormone action in metabolic regulation

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.

A Cardiac MicroRNA Governs Systemic Energy Homeostasis by Regulation of MED13

“…TH is a major determinant of metabolic rate, energy expenditure and cardiac contractility (Song et al, 2011). The global phenotype resulting from cardiac over-expression of MED13 is similar to that of enhanced TH signaling, which is associated with increased energy expenditure and resistance to fat accumulation in mice and humans (Watanabe et al, 2006).…”

“…TH signaling confers numerous beneficial effects, including increased metabolic rate, lipolysis, cholesterol lowering, improved glucose homeostasis, and enhanced cardiac function as seen in antimiR-208a treated and αMHC-Med13 TG mice (Crunkhorn and Patti, 2008; Song et al, 2011; Watanabe et al, 2006). However, hyperthyroidism is also associated with adverse effects, such as tachycardia, arrhythmias, muscle wasting and elevated body temperature, which we did not observe in these mice.…”

“…Activation of TRs directly through elevation of TH results in enhanced energy expenditure and a lean phenotype (Mitchell et al, 2010; Watanabe et al, 2006). Numerous genes involved in energy balance are controlled by TH responsive elements (TREs) and are directly activated or repressed by TRs (Song et al, 2011). Other nuclear hormone receptors, such as PPARs and retinoid X receptor (RXR), as well as their coactivators and corepressors, also control energy homeostasis by activation of lipogenic genes in the heart and other tissues (Huss and Kelly, 2004).…”

Emerging roles of the corepressors NCoR1 and SMRT in homeostasis

“…Thyroid hormone is important in growth, differentiation, and development as well as metabolic homeostasis (Song et al 2011). Thyroid …”

Circadian Regulation of Tshb Gene Expression by Rev-Erbα (NR1D1) and Nuclear Corepressor 1 (NCOR1)

“…Thyroid hormones (THs), 3 T 4 and T 3 , play an integral role in development, growth, and cellular metabolism (1)(2)(3), and circulating levels of THs are maintained within a narrow range by a finely tuned negative feedback system involving the hypothalamic-pituitary-thyroid (HPT) axis (4). Thyrotropin-releasing hormone (TRH) secreted from the hypothalamus stimulates pituitary thyrotrophs to produce biologically active thyroid stimulating hormone (TSH), which stimulates the thyroid gland to synthesize and secrete THs.…”