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Adipocyte thyroid hormone β receptor-mediated hormone action fine-tunes the intracellular glucose and lipid metabolism and systemic homeostasis

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posted on 2023-02-01, 18:11 authored by Yiruo Ma, Siyi Shen, Ying Yan, Shengjie Zhang, Shengnan Liu, Zhili Tang, Jing Yu, Mei Ma, Zhoumin Niu, Zhuoyang Li, Yuting Wu, Lin Zhao, Zhiqiang Lu, Chunchun Wei, Weiping J. Zhang, Ying Xue, Qiwei Zhai, Yu Li, Cheng Hu, Jingjing Jiang, Yuying Li, Hao Ying

Thyroid hormone (TH) has a profound effect on energy metabolism and systemic homeostasis. Adipose tissues are crucial for maintaining whole-body homeostasis, however, whether TH regulates systemic metabolic homeostasis through its action on the adipose tissues is unclear. Here, we demonstrate that systemic administration of triiodothyronine (T3), the active form of TH, affects both inguinal white adipose tissue (iWAT) and whole-body metabolism. Taking advantage of the mouse model lacking adipocyte TH receptor α (TRα) or β (TRβ) we show that TRβ is the major TR isoform that mediates the T3 action on the expression of genes involved in multiple metabolic pathways in iWAT, including glucose uptake and usage, de novo fatty acid synthesis, and both UCP1-dependent and -independent thermogenesis. Moreover, our results indicate that ChREBP in iWAT is regulated by T3, thereby being critically involved in T3-regulated glucose and lipid metabolism and energy dissipation. Meanwhile, mice with adipocyte TRβ deficiency are susceptible to diet-induced obesity and metabolic dysregulation, suggesting that TRβ in adipocytes may sever as a potential target for metabolic diseases. 

Funding

This work was supported by National Key Research and Development Program of China No. 2021YFA1100500 (H.Y.); National NSFC 91957205 (H.Y.), 82070821 (J.J.), 81970748 (L.Z.), 81870541 (Z.L.); Pujiang Talent Program from STCSM 21PJ1416100 (Y.L.); Youth Innovation Promotion Association, CAS 2021261 (Y.L.); Laboratory for Marine Drugs and Bioproducts of Pilot National Laboratory for Marine Science and Technology (Qingdao) LMDBKF-2019-04 (H.Y.); and NHC Key Laboratory of Food Safety Risk Assessment (2020K02 to Y.W.).

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