Triiodothyronine regulates distribution of thyroid hormone receptors by activating AMP-activated protein kinase in 3T3-L1 adipocytes and induces uncoupling protein-1 expression

Abstract

The purposes of this study were to examine whether thermogenesis in 3T3-L1 adipocytes is related to variations in thyroid hormone receptors (TRs) that are differently regulated by triiodothyronine (T3), and the possible role of AMP-activated protein (AMPK) in thermogenesis after cell differentiation. Differentiated 3T3-L1 adipocytes were maintained under four conditions: normal control group, T3 treatment group, AMPK agonist (5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside) treatment group, and T3 and AMPK inhibitor (Compound C) treatment group. Real-time polymerase chain reaction was then performed to evaluate the changes in TRα and TRβ mRNA levels in the cells, as well as marker genes for brown adipose tissue including uncoupling protein (UCP)-1 and Cidea. Western blotting was carried out for the cells to detect the expressions of TRα, TRβ, and AMPK protein levels. After T3 treatment, the mRNA and protein levels of TRα decreased compared with the control group, while TRβ mRNA and protein levels increased markedly at the same time. We also found elevated mRNA levels of UCP-1 and Cidea after exposure to T3. However, the distribution of TRs was reversed by Compound C. AMPK protein levels were clearly activated by T3. Our results suggest that the distribution of TRs is related to thermogenesis, and AMPK may participate in the alterations.

Pharmacological Activation of Thyroid Hormone Receptors Elicits a Functional Conversion of White to Brown Fat

“…Is WAT browning an unappreciated component of thyroid thermogenesis? As T 3 can also induce browning in vitro (Lee et al 2012; Wang et al 2014), it is certainly possible. However, since T 3 appears to be much less effective at promoting browning than GC-1, further studies will be necessary to determine whether browning is a major contributor to the thermogenesis that accompanies hyperthyroid states or simply an ancillary effect.…”

Thermal conditions experienced during differentiation affect metabolic and contractile phenotypes of mouse myotubes

“…Importantly, increased activity of AMPK can shift mouse muscle to a more oxidative metabolic phenotype with increased MHC IIa concentrations, albeit without changing MHC I content (22). Additionally, AMPK may alter expression of thyroid receptors in adipose tissue (34), although it is not known whether this is also the case in muscle cells.…”

Exogenous thyroxine improves glucose intolerance in insulin-resistant rats

“…Furthermore, T3 can increase the expression of THrβ1, which may activate (phosphorylate) AMPK, a key regulator of cellular metabolism (Cantó & Auwerx 2013, Wang et al 2014). When active, AMPK triggers the translocation of GLUT4 to the plasma membrane to increase the uptake of glucose (Cantó & Auwerx 2013).…”