Rapid Repression of ADP Transport by Palmitoyl-CoA Is Attenuated by Exercise Training in Humans: A Potential Mechanism to Decrease Oxidative Stress and Improve Skeletal Muscle Insulin Signaling.
Rapid Repression of ADP Transport by Palmitoyl-CoA Is Attenuated by Exercise Training in Humans: A Potential Mechanism to Decrease Oxidative Stress and Improve Skeletal Muscle Insulin Signaling.
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DOI：
10.2337/db14-1838
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发表时间：
2015-08
期刊：
影响因子：
7.7
通讯作者：
Holloway GP
中科院分区：
文献类型：
--
作者：
Ludzki A;Paglialunga S;Smith BK;Herbst EA;Allison MK;Heigenhauser GJ;Neufer PD;Holloway GP
线粒体ADP转运可能代表了一个融合点，统一了胰岛素抵抗发展的两个主要工作模型，因为反应性脂质（特别是棕榈酰辅酶A [P-CoA]）可以抑制ADP转运，随后增加线粒体活性氧排放。在目前的研究中，我们的目的是确定人类运动训练是否会减少线粒体ADP呼吸敏感性的P-CoA衰减。六周的运动训练增加了全身葡萄糖稳态和骨骼肌Akt信号，减少了氧化应激标志物，但没有减少最大线粒体H2 O2排放。为了确定增强的线粒体ADP转运是否有助于改善体内氧化状态，我们测定了存在和不存在P-CoA时线粒体ADP敏感性。在缺乏P-CoA的情况下，运动训练降低了线粒体ADP敏感性。相反，运动训练增加线粒体ADP敏感性与P-CoA的存在。我们进一步表明，P-CoA非竞争性抑制线粒体ADP转运和ADP的能力，以减弱线粒体H2 O2的排放。总之，目前的数据提供了一个潜在的机制，P-CoA如何有助于胰岛素抵抗，并强调运动训练的能力，以减少P-CoA衰减线粒体ADP运输。
Mitochondrial ADP transport may represent a convergence point unifying two prominent working models for the development of insulin resistance, as reactive lipids (specifically palmitoyl-CoA [P-CoA]) can inhibit ADP transport and subsequently increase mitochondrial reactive oxygen species emissions. In the current study, we aimed to determine if exercise training in humans diminished P-CoA attenuation of mitochondrial ADP respiratory sensitivity. Six weeks of exercise training increased whole-body glucose homeostasis and skeletal muscle Akt signaling and reduced markers of oxidative stress without reducing maximal mitochondrial H2O2 emissions. To ascertain if enhanced mitochondrial ADP transport contributed to the improvement in the in vivo oxidative state, we determined mitochondrial ADP sensitivity in the presence and absence of P-CoA. In the absence of P-CoA, exercise training reduced mitochondrial ADP sensitivity. In contrast, exercise training increased mitochondrial ADP sensitivity with P-CoA present. We further show that P-CoA noncompetitively inhibits mitochondrial ADP transport and the ability of ADP to attenuate mitochondrial H2O2 emission. Altogether, the current data provide a potential mechanism for how P-CoA contributes to insulin resistance and highlight the ability of exercise training to diminish P-CoA attenuation in mitochondrial ADP transport.