Triiodothyronine (T3) promotes brown fat hyperplasia via thyroid hormone receptor α mediated adipocyte progenitor cell proliferation

Shengnan Liu, Siyi Shen, Ying Yan, Chao Sun, Zhiqiang Lu, Hua Feng, Yiruo Ma, Zhili Tang, Jing Yu, Yuting Wu, Balázs Gereben, Petra Mohácsik, Csaba Fekete, Xiaoyun Feng, Feixiang Yuan, Feifan Guo, Cheng Hu, Mengle Shao, Xin Gao, Lin Zhao, Yuying Li, Jingjing Jiang () and Hao Ying ()
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Shengnan Liu: University of Chinese Academy of Sciences, Chinese Academy of Sciences, and Shanghai Jiao Tong University Affiliated Sixth People’s Hospital
Siyi Shen: University of Chinese Academy of Sciences, Chinese Academy of Sciences, and Shanghai Jiao Tong University Affiliated Sixth People’s Hospital
Ying Yan: University of Chinese Academy of Sciences, Chinese Academy of Sciences, and Shanghai Jiao Tong University Affiliated Sixth People’s Hospital
Chao Sun: University of Chinese Academy of Sciences, Chinese Academy of Sciences, and Shanghai Jiao Tong University Affiliated Sixth People’s Hospital
Zhiqiang Lu: Fudan University
Hua Feng: Chinese Academy of Sciences
Yiruo Ma: University of Chinese Academy of Sciences, Chinese Academy of Sciences, and Shanghai Jiao Tong University Affiliated Sixth People’s Hospital
Zhili Tang: University of Chinese Academy of Sciences, Chinese Academy of Sciences, and Shanghai Jiao Tong University Affiliated Sixth People’s Hospital
Jing Yu: University of Chinese Academy of Sciences, Chinese Academy of Sciences, and Shanghai Jiao Tong University Affiliated Sixth People’s Hospital
Yuting Wu: University of Chinese Academy of Sciences, Chinese Academy of Sciences, and Shanghai Jiao Tong University Affiliated Sixth People’s Hospital
Balázs Gereben: Institute of Experimental Medicine
Petra Mohácsik: Institute of Experimental Medicine
Csaba Fekete: Institute of Experimental Medicine
Xiaoyun Feng: Shanghai Jiaotong University
Feixiang Yuan: University of Chinese Academy of Sciences, Chinese Academy of Sciences, and Shanghai Jiao Tong University Affiliated Sixth People’s Hospital
Feifan Guo: University of Chinese Academy of Sciences, Chinese Academy of Sciences, and Shanghai Jiao Tong University Affiliated Sixth People’s Hospital
Cheng Hu: Shanghai Jiao Tong University Affiliated Sixth People’s Hospital
Mengle Shao: Chinese Academy of Sciences
Xin Gao: Fudan University
Lin Zhao: Fudan University
Yuying Li: University of Chinese Academy of Sciences, Chinese Academy of Sciences, and Shanghai Jiao Tong University Affiliated Sixth People’s Hospital
Jingjing Jiang: Fudan University
Hao Ying: University of Chinese Academy of Sciences, Chinese Academy of Sciences, and Shanghai Jiao Tong University Affiliated Sixth People’s Hospital

Nature Communications, 2022, vol. 13, issue 1, 1-17

Abstract: Abstract The thyroid hormone (TH)-controlled recruitment process of brown adipose tissue (BAT) is not fully understood. Here, we show that long-term treatment of T3, the active form of TH, increases the recruitment of thermogenic capacity in interscapular BAT of male mice through hyperplasia by promoting the TH receptor α-mediated adipocyte progenitor cell proliferation. Our single-cell analysis reveals the heterogeneous nature and hierarchical trajectory within adipocyte progenitor cells of interscapular BAT. Further analyses suggest that T3 facilitates cell state transition from a more stem-like state towards a more committed adipogenic state and promotes cell cycle progression towards a mitotic state in adipocyte progenitor cells, through mechanisms involving the action of Myc on glycolysis. Our findings elucidate the mechanisms underlying the TH action in adipocyte progenitors residing in BAT and provide a framework for better understanding of the TH effects on hyperplastic growth and adaptive thermogenesis in BAT depot at a single-cell level.

Date: 2022
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DOI: 10.1038/s41467-022-31154-1

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