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明确定义控制人类骨骼肌脂质和线粒体代谢中几个关键调节步骤的机制。 这些目标将通过检查生活方式操作（急性运动，慢性运动或训练和营养）对脂质和线粒体代谢的调节和能力的影响来实现。 在人类面临的广泛的身体活动（非活动与身体活动）和营养挑战（高脂肪/能量饮食与平衡饮食）中，关于骨骼肌脂质和线粒体代谢的调节的基本信息很少。该提案概述了一个积极的计划，在体内实验，检查人体骨骼肌在现实生活中的生理情况。具体而言，拟议的工作将全面研究脂肪转运到肌肉细胞和线粒体中的重要性，以满足休息，运动和营养改变状态下脂肪氧化的需求。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，这在很大程度上是在研究中。由此产生的信息将加强我们对人体骨骼肌中脂质代谢和氧化的控制以及线粒体生物发生的基本理解。这些新的基本信息将提供设计新的运动、营养和药理干预所需的知识，这些干预将导致改善肌肉功能，从而改善人类在健康和疾病中的表现。

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.