Training Effects on Skeletal Muscle Lipid Dynamics

训练对骨骼肌脂质动力学的影响

• 批准号: 9203052
• 负责人: LISA S CHOW
• 金额: $ 53.14万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-01-10 至 2018-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9203052
• 关键词: Acyl Coenzyme A; Adipose tissue; Aerobic; Aerobic Exercise; Affect; Age; American; Biopsy; Ceramides; Coupled; Data; Development; Diglycerides; Enrollment; Euglycemic Clamping; Fatty Acids; Future; Glucose; Human; Human body; Hydrolase; Incidence; Infusion procedures; Insulin Resistance; Kinetics; Label; Lipase; Lipids; Lipolysis; Measures; Metabolic; Metabolic syndrome; Mitochondria; Muscle; Non-Insulin-Dependent Diabetes Mellitus; Nonesterified Fatty Acids; Obesity; Oleates; Overweight; Palmitates; Participant; Patients; Physiologic pulse; Physiological; Play; Population; Proteins; Reactive Oxygen Species; Reporting; Respiration; Rest; Role; Serum; Site; Skeletal Muscle; Testing; Therapeutic Human Experimentation; Thinness; Training; Training Programs; Triglycerides; acylcarnitine; design; enzyme activity; experimental study; fatty acid oxidation; genetic regulatory protein; glucose metabolism; improved; innovation; insight; insulin sensitivity; lipid mediator; lipid metabolism; mRNA Expression; novel; novel therapeutics; oxidation; pigment epithelium-derived factor; preference; protein expression; public health relevance; sedentary; stable isotope; sterol esterase

DESCRIPTION (provided by applicant): 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 t 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 skeleta muscle. This study is innovative in its focus on aerobic training associated alterations in skeleta muscle lipid kinetics, particularly in the use of a cutting-edge, stable isotope, pulse-chase desig 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 that 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.

描述（由申请人提供）：骨骼肌脂质代谢的改变被认为显著促进骨骼肌胰岛素抵抗，其先于并预测2型糖尿病（T2 DM）。有氧训练被认为可以防止脂质诱导的胰岛素抵抗，即使在休息状态下。然而，我们的初步数据发现，在有氧运动的参与者中，胰岛素敏感性下降的时间早于久坐不动的参与者。 适度的FFA升高，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。许多研究已经解释了高肌肉脂质含量和高肌肉胰岛素敏感性在耐力训练的人作为减少肌肉脂质代谢物的结果，脂质诱导的胰岛素抵抗的假定介质的明显矛盾。然而，这些研究仅涉及静态测量，有氧训练如何改变肌肉脂质代谢的动力学仍然未知。本提案将研究有氧训练对久坐、超重/肥胖、胰岛素抵抗人群的脂质代谢动力学的影响，这些人群可能特别容易受到IMCL和毒性脂质代谢物蓄积的影响。我们将测试有氧训练增加静息肌肉脂质代谢的假设，如通过IMCL脂解、脂质代谢物积累和脂肪酸的线粒体利用的标志物所测量的。在目的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。在目标2中，我们计划确定有氧训练对骨骼肌脂质代谢动力学的影响。在目标3中，我们计划确定有氧训练对骨骼肌中脂肪酸线粒体利用的影响。这项研究是创新的，其重点是有氧训练相关的改变，肌肉脂质动力学，特别是在使用先进的，稳定的同位素，脉冲追踪设计，动态检查IMCL积累和脂质代谢产物。通过关注久坐、超重/肥胖、胰岛素抵抗的受试者，我们正在研究一个特别容易受到骨骼肌脂质代谢功能障碍影响的人群，他们可能会从有氧训练中显著受益。本研究的意义在于为有氧训练对骨骼肌脂质代谢的机制性益处提供重要见解，为治疗胰岛素抵抗及其导致的T2 DM并发症开辟新的方向。