Exercise and nutritional control of lipid and mitchondrial metabolism in human skeletal muscle

我的研究计划的总体目标是清楚地定义控制人类骨骼肌脂质和线粒体代谢的几个关键调控步骤的机制。这些目标将通过检查生活方式操纵（急性运动、慢性运动或训练以及营养）对脂质和线粒体代谢的调节和能力的影响来实现。关于骨骼肌脂质和线粒体代谢在人类面临的各种体力活动（不活动vs.体力活动）和营养挑战（高脂肪/能量饮食vs.均衡饮食）中的调节的基本信息很少。这一建议概述了一项积极的体内实验计划，在现实生活的生理情况下检查人类骨骼肌。具体来说，拟议的工作将全面检查脂肪转运到肌肉细胞和线粒体的重要性，以满足休息，运动和营养改变状态下脂肪氧化的需要。这项工作还将研究骨骼肌对运动训练的分子、生化和生理适应的时间过程。这项工作的重点将是人类骨骼肌，这在很大程度上已经得到了研究。由此产生的信息将增强我们对人类骨骼肌中脂质代谢和氧化的控制以及线粒体的生物发生的基本理解。这一新颖的基本信息将为设计新的运动、营养和药理学干预措施提供所需的知识，这些干预措施将改善人类在健康和疾病中的肌肉功能。

The overarching objective of my research program is to clearly define the mechanisms controlling several key regulatory steps in human skeletal muscle lipid and mitochondrial metabolism. These objectives will be realized by examining the effects of lifestyle manipulations (acute exercise, chronic exercise or training, and nutrition) on the regulation and capacity for lipid and mitochondrial metabolism. Little basic information exists regarding the regulation of skeletal muscle lipid and mitochondrial metabolism over the wide spectrums of physical activity (inactive vs. physically active) and nutritional challenges (high fat/ energy diets vs. balanced diets) that humans face. This proposal outlines an aggressive program of in vivo experiments that examine human skeletal muscle during real-life physiological situations. Specifically, the proposed work will comprehensively examine the importance of fat transport into the muscle cell and also into the mitochondria to meet the needs for fat oxidation in resting, exercise and nutritionally altered states. The work will also examine the time course of molecular, biochemical and physiological adaptations in skeletal muscle to exercise training. The focus of this work will be in human skeletal muscle, which has been largely under studied. The resulting information will enhance our basic understanding of the control of lipid metabolism and oxidation and the biogenesis of mitochondria in human skeletal muscle. This novel basic information will provide the knowledge needed to design new exercise, nutritional and pharmacological interventions that will lead to improved muscle function for human performance in health and disease.