Department of Biochemistry, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou 325035, China.
Department of Biochemistry, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou 325035, China; Center for Translational Medicine and Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing 210093, China.
Life Sci. 2018 Aug 1;206:84-92. doi: 10.1016/j.lfs.2018.05.041. Epub 2018 May 23.
High level of saturated fatty acids leads to mitochondrial dysfunction and inflammation in the development of insulin resistance in skeletal muscle. We recently found that puerarin improved impaired insulin signaling in skeletal muscle in diabetic animals and in myotubes in vitro. However, whether puerarin can act directly on muscle cells to alleviate lipid-induced mitochondrial dysfunction and inflammation remains obscure. This study was conducted to analyze the attributive properties of puerarin against mitochondrial dysfunction and inflammation in skeletal muscle cells with insulin resistance.
The effects of puerarin on mitochondrial biogenesis, oxidative phosphorylation, dynamics of fusion, fission and mitophagy, oxidative stress, as well as inflammatory response and insulin sensitivity in L6 myotubes treated with palmitate were examined.
Puerarin pretreatment improve insulin sensitivity and prevented muscle cells from palmitate-induced mitochondrial dysfunction manifested by the increases of complex I activity, mitochondrial membrane potential and ATP generation, and the decrease of reactive oxygen species (ROS) production. Augmented expression of genes involved in mitochondrial biogenesis, oxidative phosphorylation, and the detoxification of ROS were also observed upon puerarin supplementation. Moreover, puerarin modulated mitochondrial fusion and fission, and rescued palmitate-impaired mitophagy via phosphatase and tensin homolog-induced putative kinase 1(PINK1)/Parkin pathway. In addition, puerarin attenuated palmitate-induced inflammation through the inhibition of toll-like receptor 4/nuclear factor-κB signaling pathway.
Our findings indicated that puerarin could act directly on muscle cells to attenuate palmitate-induced mitochondrial dysfunction, impaired mitophagy and inflammatory response, thereby contributing to the improvement of insulin sensitivity.
高水平的饱和脂肪酸会导致线粒体功能障碍和炎症，从而导致骨骼肌胰岛素抵抗的发生。我们最近发现葛根素可改善糖尿病动物和体外肌管中胰岛素信号受损。然而，葛根素是否可以直接作用于肌肉细胞，减轻脂质诱导的线粒体功能障碍和炎症仍不清楚。本研究旨在分析葛根素对胰岛素抵抗骨骼肌细胞中线粒体功能障碍和炎症的调节作用。
研究了葛根素对棕榈酸处理的 L6 肌管中线粒体生物发生、氧化磷酸化、融合、裂变和自噬、氧化应激以及炎症反应和胰岛素敏感性的影响。
葛根素预处理可改善胰岛素敏感性，并防止肌肉细胞发生棕榈酸诱导的线粒体功能障碍，表现为复合物 I 活性、线粒体膜电位和 ATP 生成增加，活性氧（ROS）生成减少。葛根素补充还观察到与线粒体生物发生、氧化磷酸化和 ROS 解毒相关的基因表达增加。此外，葛根素通过磷酸酶和张力蛋白同源物诱导的假定激酶 1（PINK1）/Parkin 途径调节线粒体融合和裂变，并挽救棕榈酸损伤的自噬。此外，葛根素通过抑制 Toll 样受体 4/核因子-κB 信号通路减轻棕榈酸诱导的炎症。
我们的研究结果表明，葛根素可以直接作用于肌肉细胞，减轻棕榈酸诱导的线粒体功能障碍、自噬受损和炎症反应，从而改善胰岛素敏感性。
