2. Academic Validation
  3. Cellular Feimin enhances exercise performance by suppressing muscle thermogenesis

Cellular Feimin enhances exercise performance by suppressing muscle thermogenesis

  • Nat Metab. 2025 Jan;7(1):84-101. doi: 10.1038/s42255-024-01176-8.
Ying Peng # 1,  Liangjie Jia # 1,  Xiao Hu 1,  Xiaoliu Shi 1,  Xinlei Fang 1,  Yifu Qiu 2 3,  Zhenji Gan 4,  Yiguo Wang 5
Affiliations

Affiliations

  • 1 State Key Laboratory of Membrane Biology, MOE Key Laboratory of Bioinformatics, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China.
  • 2 Institute of Molecular Medicine, College of Future Technology, Peking University, Beijing, China.
  • 3 Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.
  • 4 State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Medical School of Nanjing University, Nanjing, China.
  • 5 State Key Laboratory of Membrane Biology, MOE Key Laboratory of Bioinformatics, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China. yiguo@mail.tsinghua.edu.cn.
  • # Contributed equally.
PMID: 39747484 DOI: 10.1038/s42255-024-01176-8
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.

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