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.
Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Nat Commun. 2022 Jun 13;13(1):3394. doi: 10.1038/s41467-022-31154-1.
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.
甲状腺激素（TH）控制棕色脂肪组织（BAT）的募集过程尚未完全阐明。在这里，我们表明，T3（TH 的活性形式）的长期治疗通过促进 TH 受体α介导的脂肪祖细胞增殖来增加雄性小鼠肩胛间 BAT 的产热能力募集，从而增加产热能力募集。我们的单细胞分析揭示了肩胛间 BAT 脂肪祖细胞的异质性和层次轨迹。进一步的分析表明，T3 通过 Myc 对糖酵解的作用，促进细胞状态从更类似于干细胞的状态向更确定的脂肪生成状态转变，并促进脂肪祖细胞向有丝分裂状态的细胞周期进展，从而促进细胞状态转变。我们的研究结果阐明了 TH 在 BAT 中驻留的脂肪祖细胞中的作用机制，并为更好地理解 TH 在 BAT 库中的增生性生长和适应性产热的影响提供了一个在单细胞水平上的框架。
