Haohao Zhang, Guijun Qin, Juan Zheng, Wen Kong, Lulu Chen
Division of Endocrinology, Department of Internal Medicine, The First Affiliated Hospital of Zhengzhou University, 40 Daxue Road, Zhengzhou, 450052, People's Republic of China,
J Physiol Biochem. 2015 Mar;71(1):121-31. doi: 10.1007/s13105-015-0392-1. Epub 2015 Feb 17.
Although resveratrol (RES) is thought to be a key regulator of insulin sensitivity in rodents, the exact mechanism underlying this effect remains unclear. Therefore, we sought to investigate how RES affects skeletal muscle oxidative and antioxidant levels of subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondrial populations in high-fat diet (HFD)-induced insulin resistance (IR) rats. Systemic and skeletal muscle insulin sensitivity together with expressions of several genes related to mitochondrial biogenesis and skeletal muscle SIRT1, SIRT3 protein levels were studied in rats fed a normal diet, a HFD, and a HFD with intervention of RES for 8 weeks. Oxidative stress levels and antioxidant enzyme activities were assessed in SS and IMF mitochondria. HFD fed rats exhibited obvious systemic and skeletal muscle IR as well as decreased SIRT1 and SIRT3 expressions, mitochondrial DNA (mtDNA), and mitochondrial biogenesis (p < 0.05). Both SS and IMF mitochondria demonstrated elevated reactive oxygen species (ROS) and malondialdehyde (MDA) levels. In addition, SS mitochondrial antioxidant enzyme activities were significantly lower, while IMF mitochondrial antioxidant enzyme activities were higher (p < 0.05). By contrast, RES treatment protected rats against diet induced IR, increased SIRT1 and SIRT3 expressions, mtDNA, and mitochondrial biogenesis (p < 0.05). Moreover, the activities of SS and IMF mitochondrial antioxidant enzymes were increased, which reverted the increased SS mitochondrial oxidative stress levels (p < 0.05). This study suggests that RES ameliorates insulin sensitivity consistent with improved SIRT3 expressions and rebalance between SS mitochondrial oxidative stress and antioxidant competence in HFD rats.
尽管白藜芦醇（RES）被认为是啮齿动物胰岛素敏感性的关键调节因子，但其作用的确切机制仍不清楚。因此，我们试图研究RES如何影响高脂饮食（HFD）诱导的胰岛素抵抗（IR）大鼠肌膜下（SS）和肌原纤维间（IMF）线粒体群体的骨骼肌氧化和抗氧化水平。在喂食正常饮食、HFD以及接受RES干预8周的HFD大鼠中，研究了全身和骨骼肌胰岛素敏感性以及与线粒体生物发生相关的几个基因的表达和骨骼肌SIRT1、SIRT3蛋白水平。评估了SS和IMF线粒体中的氧化应激水平和抗氧化酶活性。喂食HFD的大鼠表现出明显的全身和骨骼肌IR，以及SIRT1和SIRT3表达、线粒体DNA（mtDNA）和线粒体生物发生减少（p<0.05）。SS和IMF线粒体均显示活性氧（ROS）和丙二醛（MDA）水平升高。此外，SS线粒体抗氧化酶活性显著降低，而IMF线粒体抗氧化酶活性较高（p<0.05）。相比之下，RES治疗可保护大鼠免受饮食诱导的IR，增加SIRT1和SIRT3表达、mtDNA和线粒体生物发生（p<0.05）。此外，SS和IMF线粒体抗氧化酶的活性增加，这逆转了SS线粒体氧化应激水平的升高（p<0.05）。本研究表明，RES改善胰岛素敏感性，这与HFD大鼠中SIRT3表达的改善以及SS线粒体氧化应激与抗氧化能力之间的重新平衡一致。
