Thyroid hormones, including 3,5,3′‐triiodothyronine (T3), cause a wide spectrum of genomic effects on cellular metabolism and bioenergetic regulation in various tissues. The nongenomic actions of T3 have been reported but are not yet completely understood. Acute T3 treatment significantly enhanced basal, maximal, ATP‐linked, and proton‐leak oxygen consumption rates (OCRs) of primary differentiated mouse brown adipocytes accompanied with increased protein abundances of uncoupling protein 1 (UCP1) and mitochondrial Ca2+ uniporter (MCU). T3 treatment depolarized the resting mitochondrial membrane potential (Ψm) but augmented oligomycininduced hyperpolarization in brown adipocytes. Protein kinase B (AKT) and mammalian target of rapamycin (mTOR) were activated by T3, leading to the inhibition of autophagic degradation. Rapamycin, as an mTOR inhibitor, blocked T3‐induced autophagic suppression and UCP1 upregulation. T3 increases intracellular Ca2+ concentration ([Ca2+]i) in brown adipocytes. Most of the T3 effects, including mTOR activation, UCP1 upregulation, and OCR increase, were abrogated by intracellular Ca2+ chelation with BAPTA‐AM. Calmodulin inhibition with W7 or knockdown of MCU dampened T3‐induced mitochondrial activation. Furthermore, edelfosine, a phospholipase C (PLC) inhibitor, prevented T3 from acting on [Ca2+]i, UCP1 abundance, Ψm, and OCR. We suggest that short‐term exposure of T3 induces UCP1 upregulation and mitochondrial activation due to PLC‐mediated [Ca2+]i elevation in brown adipocytes.
|Journal||International journal of molecular sciences|
|Publication status||Published - 2021 Aug 2|
Bibliographical noteFunding Information:
Funding: This work was supported by the Medical Research Center Program (2017R1A5A2015369) and Bio & Medical Technology Development Program (2020M3A9D8039920) from the Ministry of Science, ICT, Korea
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Computer Science Applications
- Physical and Theoretical Chemistry
- Organic Chemistry
- Inorganic Chemistry