5-十七烷基间苯二酚通过 SIRT3 介导的线粒体自噬改善肥胖相关的骨骼肌线粒体功能障碍,Journal of Agricultural and Food Chemistry

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5-十七烷基间苯二酚通过 SIRT3 介导的线粒体自噬改善肥胖相关的骨骼肌线粒体功能障碍
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2023-10-20 , DOI: 10.1021/acs.jafc.3c01452
Ziyuan Wang _{1,

2} , Qing Li ₁ , Haihong Yang ₁ , Dandan Zhang ₁ , Yiman Zhang ₁ , Jing Wang _{1,

2} , Jie Liu _{1,

2}

Affiliation

肥胖引起的骨骼肌功能障碍的特点是线粒体含量和功能下降。5-十七烷基间苯二酚 (AR-C17) 是一种源自全麦和黑麦的特定生物活性成分，已被证明可以改善与肥胖相关的骨骼肌失调。然而，其保护活性的机制需要进一步探索。在此，我们发现 AR-C17（5、10 和 20 μM）干预逆转了 PA 诱导的 C2C12 细胞中线粒体含量、线粒体膜电位和线粒体能量代谢的减少（0.5 mM）。同时，AR-C17通过提高线粒体自噬通量和上调自噬相关蛋白的表达水平，明显减轻PA介导的肌管线粒体功能障碍，而这种作用被自噬抑制剂（3-MA）消除。进一步分析表明，SIRT3-FOXO3A-PINK-Parkin 介导的线粒体自噬参与 AR-C17 对心肌细胞线粒体功能障碍的调节。此外，AR-C17 给药（30 和 150 mg/kg/天）通过 SIRT3 依赖性线粒体自噬显着改善了小鼠骨骼肌组织中高脂肪饮食诱导的线粒体失调。我们的研究结果表明，骨骼肌细胞对 AR-C17 有反应，从而在体外和体内改善肌生成和线粒体自噬。

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5-Heptadecylresorcinol Ameliorates Obesity-Associated Skeletal Muscle Mitochondrial Dysfunction through SIRT3-Mediated Mitophagy

Skeletal muscle dysfunction caused by obesity is characterized by the decline in mitochondrial content and function. 5-Heptadecylresorcinol (AR-C17) is a specific bioactive component derived from whole wheat and rye, which has been evidenced to improve obesity-associated skeletal muscle dysregulation. However, the mechanism underlying its protective activity requires further exploration. Herein, we found that AR-C17 (5, 10, and 20 μM) intervention reversed PA-induced (0.5 mM) reduction in mitochondrial content, mitochondrial membrane potential, and mitochondrial energy metabolism in C2C12 cells. Meanwhile, AR-C17 evidently alleviated PA-mediated myotube mitochondrial dysfunction via elevating mitochondria autophagy flux and upregulating the expression level of autophagy-related protein, while this effect was abolished by an autophagy inhibitor (3-MA). Further analysis showed that SIRT3-FOXO3A-PINK-Parkin-mediated mitophagy was involved in the modulation of myocyte mitochondrial dysfunction by AR-C17. In addition, AR-C17 administration (30 and 150 mg/kg/day) significantly improved high-fat-diet-induced mitochondrial dysregulation in mice skeletal muscle tissue via SIRT3-dependent mitophagy. Our findings indicate that skeletal muscle cells are responsive to AR-C17, which improves myogenesis and mitophagy in vitro and in vivo.

更新日期：2023-10-20

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