Synergy in free radical generation is blunted by high-fat diet induced alterations in skeletal muscle mitochondrial metabolism.
Synergy in free radical generation is blunted by high-fat diet induced alterations in skeletal muscle mitochondrial metabolism.
复制标题
高脂肪饮食引起的骨骼肌线粒体代谢变化削弱了自由基产生的协同作用。
DOI：
10.1016/j.bpj.2013.01.025
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发表时间：
2013
影响因子：
3.4
通讯作者：
Periwal,Vipul
中科院分区：
文献类型：
--
作者：
Li,Yanjun;Periwal,Vipul
由于它们在细胞能量学和代谢中的作用，骨骼肌线粒体似乎在胰岛素抵抗和II型糖尿病的发展中起关键作用。高脂饮食可诱导较高水平的活性氧（ROS），表现为线粒体释放过氧化氢（H2 O2），这可能是骨骼肌胰岛素抵抗的原因。潜在的机制尚不清楚。最近发表的关于骨骼肌在正常饮食（CON）和高脂饮食（HFD）状态下的单一底物（丙酮酸、琥珀酸、脂肪）代谢的数据使我们能够开发骨骼肌线粒体代谢的综合数学模型。模型模拟表明，长期HFD可能会影响特定的代谢反应/途径，通过改变酶的活性。我们的模型使我们能够预测氧气消耗和ROS生成的任何组合的基板。特别是，我们预测之间的协同作用（等膜电位）丙酮酸和脂肪的组合在ROS生产相比，ROS生产的总和与每个基板单独在CON和HFD状态。这种协同作用在HFD状态下减弱。
Due to their role in cellular energetics and metabolism, skeletal muscle mitochondria appear to play a key role in the development of insulin resistance and type II diabetes. High-fat diet can induce higher levels of reactive oxygen species (ROS), evidenced by hydrogen peroxide (H2O2) emission from mitochondria, which may be causal for insulin resistance in skeletal muscle. The underlying mechanisms are unclear. Recent published data on single substrate (pyruvate, succinate, fat) metabolism in both normal diet (CON) and high-fat diet (HFD) states of skeletal muscle allowed us to develop an integrated mathematical model of skeletal muscle mitochondrial metabolism. Model simulations suggested that long-term HFD may affect specific metabolic reaction/pathways by altering enzyme activities. Our model allows us to predict oxygen consumption and ROS generation for any combination of substrates. In particular, we predict a synergy between (iso-membrane potential) combinations of pyruvate and fat in ROS production compared to the sum of ROS production with each substrate singly in both CON and HFD states. This synergy is blunted in the HFD state.