Berberine suppressed sarcopenia insulin resistance through SIRT1-mediated mitophagy

Abstract 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.