Triiodothyronine (T3) promotes brown fat hyperplasia via thyroid hormone receptor α mediated adipocyte progenitor cell proliferation PMID: 35697700

ADC Targets in Oncology

2026-04-10

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

Nat Commun. 2022 Jun 13;13(1):3394. doi: 10.1038/s41467-022-31154-1.

Shengnan Liu ^# ¹ , Siyi Shen ^# ¹ , Ying Yan ¹ , Chao Sun ¹ , Zhiqiang Lu ² ³ , Hua Feng ⁴ , Yiruo Ma ¹ , Zhili Tang ¹ , Jing Yu ¹ , Yuting Wu ¹ , Balázs Gereben ⁵ , Petra Mohácsik ⁵ , Csaba Fekete ⁶ , Xiaoyun Feng ⁷ , Feixiang Yuan ¹ , Feifan Guo ¹ , Cheng Hu ⁸ , Mengle Shao ⁹ , Xin Gao ² ³ , Lin Zhao ² ³ , Yuying Li ¹ , Jingjing Jiang ¹⁰ ¹¹ , Hao Ying ¹² ¹³ ¹⁴

Affiliations

1. CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, and Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
2. Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
3. Fudan Institute for Metabolic Diseases, Fudan University, Shanghai, China.
4. Omics Core, Bio-Med Big Data Center, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai, 200031, China.
5. Laboratory of Molecular Cell Metabolism, Institute of Experimental Medicine, Budapest, 1083, Hungary.
6. Laboratory of Integrative Neuroendocrinology, Institute of Experimental Medicine, Budapest, 1083, Hungary.
7. Department of Endocrinology and Metabolism, Shanghai General Hospital, School of medicine, Shanghai Jiaotong University, Shanghai, 200080, China.
8. Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Centre for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
9. The Center for Microbes, Development and Health, Institute Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, 200031, China.
10. Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, 200032, China. [email protected].
11. Fudan Institute for Metabolic Diseases, Fudan University, Shanghai, China. [email protected].
12. CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, and Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. [email protected].
13. Innovation Center for Intervention of Chronic Disease and Promotion of Health, Shanghai, China. [email protected].
14. Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing, 100021, China. [email protected].
# Contributed equally.

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.