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With advancing age, the incidence of sarcopenia increases, eventually leading to a cascade of adverse events. However, there is currently a lack of effective pharmacological treatment for sarcopenia. Sodium-glucose co-transporter 2 inhibitor (SGLT2i) empagliflozin demonstrates anti-fibrotic capabilities in various organs. This study aims to determine whether empagliflozin can improve skeletal muscle fibrosis induced by sarcopenia in naturally aging mice. A natural aging model was established by feeding male mice from 13 months of age to 19 months of age. A fibrosis model was created by stimulating skeletal muscle fibroblasts with TGF-β1. The Forelimb grip strength test assessed skeletal muscle function, and expression levels of COL1A1, COL3A1, and α-SMA were analyzed by western blot, qPCR, and immunohistochemistry. Additionally, levels of AMPKα/MMP9/TGFβ1/Smad signaling pathways were examined. In naturally aging mice, skeletal muscle function declines, expression of muscle fibrosis markers increases, AMPKα expression is downregulated, and MMP9/TGFβ1/Smad signaling pathways are upregulated. However, treatment with empagliflozin reverses this phenomenon. At the cellular level, empagliflozin exhibits similar anti-fibrotic effects, and these effects are attenuated by Compound C and siAMPKα. Empagliflozin exhibits anti-fibrotic effects, possibly associated with the AMPK/MMP9/TGFβ1/Smad signaling pathways.
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Data analyzed during the study is not publicly available but can be available on request to corresponding author.
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Funding
This work was supported by the research fund from Chongqing Municipal Health Commission (Grant No. CQYC2020020331), and Chongqing Municipal Bureau of Science and Technology (Grant No. cstc2021ycjh-bgzxm0050).
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QXH, JC: performed the experiment. QXH, JC: performed the data collection and wrote the manuscript. SQL, JCL, RHF, YSH and PYC: contributed significantly to analysis. DFL: designed the entire experiment and directed the conduct of this search. All the contributing authors scrutinized and approved this paper.
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Huang, Q., Chen, J., Liao, S. et al. The SGLT2 inhibitor empagliflozin inhibits skeletal muscle fibrosis in naturally aging male mice through the AMPKα/MMP9/TGF-β1/Smad pathway. Biogerontology (2024). https://doi.org/10.1007/s10522-024-10093-y
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DOI: https://doi.org/10.1007/s10522-024-10093-y