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<p>Squalene, a polyunsaturated triterpene and sterol precursor present in shark liver oil, was evaluated for its protective effects against skeletal muscle atrophy. This study examined its effects in both tumor necrosis factor-alpha (TNF-α)-treated C2C12 myotubes and in a mouse model of immobilization-induced muscle atrophy. After 7&#xa0;days of immobilization, C57BL/6J mice received daily oral squalene (100 or 200&#xa0;mg/kg) or saline for 7&#xa0;days. Squalene alleviated muscle atrophy, as evidenced by increases in grip strength, muscle mass, and muscle fiber cross-sectional area. Mechanistically, squalene activated the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway to promote protein synthesis and suppressed forkhead box O3a-mediated protein degradation by downregulating muscle-specific E3 ubiquitin ligases. Furthermore, squalene enhanced antioxidant enzyme and reduced pro-inflammatory cytokines via inhibition of nuclear factor kappa B phosphorylation. These findings suggest that squalene attenuates muscle atrophy and improves muscle function primarily through modulation of the PI3K/Akt signaling pathway.</p>

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Squalene mitigates muscle atrophy via the PI3K/Akt pathway in TNF-α-stimulated C2C12 myotubes and immobilization-induced C57BL/6J mice

  • 期刊论文

  • 发表日期：

    2025年12月6日

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  • Yeeun Kim,
  • Mi-Bo Kim,
  • Seungok Lee,
  • Sang Gil Lee,
  • Jae-Kwan Hwang

摘要

Squalene, a polyunsaturated triterpene and sterol precursor present in shark liver oil, was evaluated for its protective effects against skeletal muscle atrophy. This study examined its effects in both tumor necrosis factor-alpha (TNF-α)-treated C2C12 myotubes and in a mouse model of immobilization-induced muscle atrophy. After 7 days of immobilization, C57BL/6J mice received daily oral squalene (100 or 200 mg/kg) or saline for 7 days. Squalene alleviated muscle atrophy, as evidenced by increases in grip strength, muscle mass, and muscle fiber cross-sectional area. Mechanistically, squalene activated the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway to promote protein synthesis and suppressed forkhead box O3a-mediated protein degradation by downregulating muscle-specific E3 ubiquitin ligases. Furthermore, squalene enhanced antioxidant enzyme and reduced pro-inflammatory cytokines via inhibition of nuclear factor kappa B phosphorylation. These findings suggest that squalene attenuates muscle atrophy and improves muscle function primarily through modulation of the PI3K/Akt signaling pathway.