Su Xiaojuan, Yang Danqi, Hu Yu, Yuan Ying, Song Le
Department of Geriatric, Zhongshan Hospital (Xiamen), Fudan University, Xiamen 361015, China.
Department of Geriatric, Zhongshan Hospital, Fudan University, No. 180, Fenglin Road, Xuhui District, Shanghai 200032, China.
Open Life Sci. 2023 Jul 17;18(1):20220648. doi: 10.1515/biol-2022-0648. eCollection 2023.
Abnormal mitochondrial function resulting in inadequate energy supply leads to sarcopenia and IR, suggesting that maintaining mitochondrial homeostasis by regulating mitophagy may be a promising strategy for sarcopenia IR therapy. Herein, we constructed sarcopenia mice model, which was treated with berberine and/or SIRT1/mitophagy inhibitors, and the activity of SIRT1/mitophagy signaling pathway was identified. Then, muscle tissue, blood biochemical index, inflammatory factors, GTT, and ITT were detected. We found that berberine treatment increased the body weight and alleviated d-galactose-induced weight loss in mice. SIRT1/mitophagy inhibitors suppressed the effects of berberine in the treatment of sarcopenia. The effect of berberine on the increase of muscle tissue, improving metabolic disorders, reducing the expression of inflammatory factors, and suppressing sarcopenia insulin resistance (IR) were reversed by SIRT1/mitophagy inhibitors. Our study establishes proof-of-concept to distinct the effect of berberine in sarcopenia IR, and provides strong evidence to support the hypothesis that berberine-induced SIRT1 triggers mitochondrial autophagy pathway and suppresses IR in sarcopenia.
线粒体功能异常导致能量供应不足会引发肌肉减少症和胰岛素抵抗（IR），这表明通过调节线粒体自噬来维持线粒体稳态可能是治疗肌肉减少症性IR的一种有前景的策略。在此，我们构建了肌肉减少症小鼠模型，用黄连素和/或SIRT1/线粒体自噬抑制剂对其进行处理，并鉴定了SIRT1/线粒体自噬信号通路的活性。然后，检测肌肉组织、血液生化指标、炎症因子、葡萄糖耐量试验（GTT）和胰岛素耐量试验（ITT）。我们发现黄连素治疗可增加小鼠体重，并减轻d-半乳糖诱导的小鼠体重减轻。SIRT1/线粒体自噬抑制剂抑制了黄连素在治疗肌肉减少症中的作用。SIRT1/线粒体自噬抑制剂逆转了黄连素对增加肌肉组织、改善代谢紊乱、降低炎症因子表达以及抑制肌肉减少症胰岛素抵抗（IR）的作用。我们的研究为明确黄连素在肌肉减少症性IR中的作用建立了概念验证，并提供了有力证据来支持黄连素诱导的SIRT1触发线粒体自噬途径并抑制肌肉减少症中IR的假说。
