Antioxidants prevent health-promoting effects of physical exercise in humans
Antioxidants prevent health-promoting effects of physical exercise in humans
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DOI：
10.1073/pnas.0903485106
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发表时间：
2009-05-26
影响因子：
11.1
通讯作者：
Blueher, Matthias
中科院分区：
文献类型：
--
作者：
Ristow, Michael;Zarse, Kim;Blueher, Matthias
运动可以延长寿命，改善2型糖尿病和胰岛素抵抗。然而，运动也会增加线粒体中可能有害的活性氧（ROS）的形成。抗氧化剂被广泛用作补充剂，但它们是否会影响运动对健康的促进作用尚不清楚。我们评估了维生素C（1000 mg/天）和维生素E（400 IU/天）联合使用对高胰岛素、正葡萄糖钳夹期间胰岛素敏感性（GIR）的影响。在4周的体育锻炼干预之前和之后，测定GIR，并获得用于基因表达分析的肌肉活检以及血浆样品，以比较相对于基线的变化和维生素对锻炼效果的潜在影响。运动增加胰岛素敏感性参数（GIR和血浆脂联素），只有在没有抗氧化剂的情况下，在先前未经训练（P < 0.001）和预先训练（P < 0.001）的个人。与此同时，仅在不存在抗氧化剂的情况下，胰岛素敏感性和ROS防御能力的ROS敏感性转录调节因子、过氧化物酶体增殖物激活受体γ（PPAR γ）以及PPAR γ共激活因子PGC 1 α和PGC 1 β的表达增加（P < 0.001）。内源性ROS防御的分子介质（超氧化物歧化酶1和2;谷胱甘肽过氧化物酶）也被运动诱导，这种作用也被抗氧化剂补充剂阻断。与有丝分裂兴奋的概念相一致，运动诱导的氧化应激改善胰岛素抵抗，并引起促进内源性抗氧化防御能力的适应性反应。补充抗氧化剂可能会妨碍人体运动的这些健康促进作用。
Exercise promotes longevity and ameliorates type 2 diabetes mellitus and insulin resistance. However, exercise also increases mitochondrial formation of presumably harmful reactive oxygen species (ROS). Antioxidants are widely used as supplements but whether they affect the health-promoting effects of exercise is unknown. We evaluated the effects of a combination of vitamin C (1000 mg/day) and vitamin E (400 IU/day) on insulin sensitivity as measured by glucose infusion rates (GIR) during a hyperinsulinemic, euglycemic clamp in previously untrained (n = 19) and pretrained (n = 20) healthy young men. Before and after a 4 week intervention of physical exercise, GIR was determined, and muscle biopsies for gene expression analyses as well as plasma samples were obtained to compare changes over baseline and potential influences of vitamins on exercise effects. Exercise increased parameters of insulin sensitivity (GIR and plasma adiponectin) only in the absence of antioxidants in both previously untrained (P < 0.001) and pretrained (P < 0.001) individuals. This was paralleled by increased expression of ROS-sensitive transcriptional regulators of insulin sensitivity and ROS defense capacity, peroxisome-proliferator-activated receptor gamma (PPAR gamma), and PPAR gamma coactivators PGC1 alpha and PGC1 beta only in the absence of antioxidants (P < 0.001 for all). Molecular mediators of endogenous ROS defense (superoxide dismutases 1 and 2; glutathione peroxidase) were also induced by exercise, and this effect too was blocked by antioxidant supplementation. Consistent with the concept of mitohormesis, exercise-induced oxidative stress ameliorates insulin resistance and causes an adaptive response promoting endogenous antioxidant defense capacity. Supplementation with antioxidants may preclude these health-promoting effects of exercise in humans.