Cellular Feimin enhances exercise performance by suppressing muscle thermogenesis

IF 18.9 1区医学 Q1 ENDOCRINOLOGY & METABOLISM

Nature metabolism Pub Date : 2025-01-02 DOI:10.1038/s42255-024-01176-8

Ying Peng, Liangjie Jia, Xiao Hu, Xiaoliu Shi, Xinlei Fang, Yifu Qiu, Zhenji Gan, Yiguo Wang

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Abstract

Exercise can rapidly increase core body temperature, and research has indicated that elevated internal body temperature can independently contribute to fatigue during physical activity. However, the precise mechanisms responsible for regulating thermogenesis in muscles during exercise have remained unclear. Here, we demonstrate that cellular Feimin (cFeimin) enhances exercise performance by inhibiting muscle thermogenesis during physical activity. Mechanistically, we found that AMP-activated protein kinase (AMPK) phosphorylates cFeimin and facilitates its translocation into the cell nucleus during exercise. Within the nucleus, cFeimin binds to the forkhead transcription factor FOXC2, leading to the suppressed expression of sarcolipin (Sln), which is a key regulator of muscle thermogenesis. In addition, our results further reveal that short-term AMPK agonist treatments can enhance exercise performance through the activation of the AMPK–cFeimin signalling pathway. In summary, these results underscore the crucial role of cFeimin in enhancing exercise performance by modulating SLN-mediated thermogenesis. The authors uncover the role of cellular Feimin in regulating exercise performance by modulating SLN-mediated muscle thermogenesis.

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细胞肺敏通过抑制肌肉产热来提高运动表现

运动可以迅速提高核心体温，研究表明，体内温度升高可以独立地导致体力活动期间的疲劳。然而，运动过程中调节肌肉产热的确切机制仍不清楚。在这里，我们证明了细胞Feimin （cFeimin）通过抑制身体活动期间的肌肉产热来提高运动表现。在机制上，我们发现amp激活的蛋白激酶（AMPK）磷酸化cFeimin，并促进其在运动过程中转运到细胞核中。在细胞核内，cFeimin与叉头转录因子FOXC2结合，导致肌colipin （Sln）的表达受到抑制，肌colipin是肌肉产热的关键调节因子。此外，我们的研究结果进一步揭示了短期AMPK激动剂治疗可以通过激活AMPK - cfeimin信号通路来提高运动表现。总之，这些结果强调了cFeimin通过调节sln介导的产热作用来提高运动表现的关键作用。

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来源期刊

Nature metabolism ENDOCRINOLOGY & METABOLISM-

CiteScore

27.50

自引率

2.40%

发文量

170

期刊介绍： Nature Metabolism is a peer-reviewed scientific journal that covers a broad range of topics in metabolism research. It aims to advance the understanding of metabolic and homeostatic processes at a cellular and physiological level. The journal publishes research from various fields, including fundamental cell biology, basic biomedical and translational research, and integrative physiology. It focuses on how cellular metabolism affects cellular function, the physiology and homeostasis of organs and tissues, and the regulation of organismal energy homeostasis. It also investigates the molecular pathophysiology of metabolic diseases such as diabetes and obesity, as well as their treatment. Nature Metabolism follows the standards of other Nature-branded journals, with a dedicated team of professional editors, rigorous peer-review process, high standards of copy-editing and production, swift publication, and editorial independence. The journal has a high impact factor, has a certain influence in the international area, and is deeply concerned and cited by the majority of scholars.