Training Effects on Skeletal Muscle Lipid Dynamics

项目摘要/摘要 骨骼肌脂代谢的改变被认为对骨骼肌有重要作用 胰岛素抵抗，它是2型糖尿病(T2 DM)的先兆和预兆。有氧训练被认为可以保护 抗脂质诱导的胰岛素抵抗，即使在休息状态下也是如此。然而，我们的初步数据发现，胰岛素 在适度的FFA中，有氧训练的参与者比久坐的参与者敏感度下降得更早 升高，这表明有氧训练可能会促进脂肪的利用，当葡萄糖和脂肪都 可用。大量研究已经解释了高肌脂含量和高肌脂含量的明显悖论 耐力训练人群肌肉胰岛素敏感性是肌肉脂肪代谢物减少的结果， 被认为是脂类诱导胰岛素抵抗的介质。然而，这些研究只涉及静态 目前尚不清楚有氧训练如何改变肌肉脂肪代谢的动态变化。 本研究旨在研究有氧训练对久坐不动的人脂代谢动力学的影响。 超重/肥胖、胰岛素抵抗的人，他们可能特别容易受到IMCL和 有毒的脂类代谢产物堆积。我们将检验有氧训练增加休息肌肉的假设。 脂代谢，通过IMCL脂解、脂代谢产物积累和 线粒体对脂肪酸的利用。 在目标1中，我们计划确定有氧训练对骨骼肌IMCL脂解标志物的影响。在……里面 目的研究有氧训练对骨骼肌脂代谢产物动力学的影响。在AIM 3、我们计划确定有氧训练对骨骼肌线粒体利用脂肪酸的影响。 这项研究在有氧训练相关骨骼肌脂类变化方面具有创新性。 动力学，特别是在使用尖端的、稳定的同位素、脉冲追逐设计来动态检查 IMCL蓄积和脂质代谢产物。通过专注于久坐、超重/肥胖、胰岛素抵抗 受试者，我们正在研究一个特别容易受到骨骼肌脂类失调影响的人群。 新陈代谢的人可能会从有氧训练中显著受益。这项研究的意义将是提供 有氧训练对骨骼肌脂代谢机制益处的重要见解 治疗2型糖尿病胰岛素抵抗及其并发症的新方向。

PROJECT SUMMARY/ABSTRACT Alteration in skeletal muscle lipid metabolism is thought to significantly contribute to skeletal muscle insulin resistance, which precedes and predicts type 2 diabetes (T2DM). Aerobic training is believed to protect against lipid induced insulin resistance, even in the resting state. Yet, our preliminary data found that insulin sensitivity declines earlier in aerobically trained participants than sedentary participants during modest FFA elevation, suggesting that aerobic training may promote lipid utilization when both glucose and lipid are available. Numerous studies have explained the apparent paradox of high muscle lipid content and high muscle insulin sensitivity in endurance trained humans as a consequence of reduced muscle lipid metabolites, the presumed mediator of lipid induced insulin resistance. However, these studies have only involved static measures and it remains unknown how aerobic training may alter the dynamics of muscle lipid metabolism. This proposal will study the aerobic training effect on lipid metabolism dynamics in sedentary, overweight/obese, insulin resistant humans, who may be particularly susceptible to the effects of IMCL and toxic lipid metabolites accumulation. We will test the hypothesis that aerobic training increases resting muscle lipid metabolism, as measured by markers of IMCL lipolysis, accumulation of lipid metabolites and mitochondrial utilization of fatty acids. In Aim 1, we plan to identify aerobic training effects on markers of skeletal muscle IMCL lipolysis. In Aim 2, we plan to identify aerobic training effects on the dynamics of skeletal muscle lipid metabolites. In Aim 3, we plan to identify aerobic training effects on mitochondrial utilization of fatty acids in skeletal muscle. This study is innovative in its focus on aerobic training associated alterations in skeletal muscle lipid kinetics, particularly in the use of a cutting-edge, stable isotope, pulse-chase design to dynamically examine IMCL accumulation and lipid metabolites. By focusing on sedentary, overweight/obese, insulin resistant subjects, we are studying a population particularly susceptible to dysfunctional skeletal muscle lipid metabolism who may significantly benefit from aerobic training. The significance of this study will be to provide important insights into the mechanistic benefit of aerobic training on skeletal muscle lipid metabolism, opening new directions for treatment of insulin resistance and its consequent complications of T2DM.