Nutritional and Contractile Regulation of Muscle Growth

描述(申请人提供)：本项目的重点是研究调节人类骨骼肌生长的生理机制。肌肉萎缩是许多疾病的常见现象，如癌症、艾滋病、创伤、脓毒症、肾衰竭，在老年人中尤其普遍。肌肉质量的丧失会导致全身虚弱、行动不便和身体依赖，并可能导致对压力的反应受损，这与感染、手术和创伤期间较高的死亡率有关。 营养和耐力运动是骨骼肌蛋白质合成代谢的两个主要刺激因素。我们的一般假设是，蛋白质合成代谢反应的大小将由这两个刺激之间的相互作用决定。特别是，我们认为骨骼肌蛋白质的增加既取决于营养刺激与运动相关的时间，也取决于营养刺激提供的能量。我们进一步假设，在营养刺激或肌肉收缩后，肌肉蛋白质合成代谢反应在健康的年轻男性中将比年轻女性更明显。 具体目标：(1)确定在一轮阻力运动之前或之后给予营养刺激时，骨骼肌蛋白质合成和净蛋白质合成的急性反应的大小。(2)确定骨骼肌蛋白质合成和净蛋白质合成对营养刺激的急性反应的大小，以提供与运动诱导的能量消耗相匹配或超过的能量。(3)探讨男女在抗阻运动前后对骨骼肌蛋白质合成反应、蛋白质合成氨基酸利用效率、亮氨酸氧化和净蛋白质合成的反应以及与营养刺激联合作用的差异。 意义重大。这些研究将提供对调节人类肌肉蛋白质平衡的生理机制的洞察，并将被用作开发基于科学的干预措施的基础，以改善衰老、创伤、癌症和艾滋病等情况下的肌肉蛋白质平衡。

DESCRIPTION (provided by applicant): The focus of this project is to examine physiological mechanisms that regulate human skeletal muscle growth. Muscle wasting is a common phenomenon in many conditions, such as cancer, AIDS, trauma, sepsis, kidney failure, and is also particularly prevalent in the elderly. The loss of muscle mass leads to overall weakness, immobility and physical dependence, and can be responsible for an impaired response to stress, which is associated with higher mortality rates during infection, surgery, and trauma. Nutrition and resistance exercise are two major protein anabolic stimuli for skeletal muscle. Our general hypothesis is that the magnitude of the protein anabolic response will be determined by the reciprocal interactions between these two stimuli. In particular, we propose that skeletal muscle protein accretion is dependent upon both the timing of the nutritional stimulus in relation to the exercise bout and the amount of energy provided by the nutritional stimulus. We further hypothesize that the muscle protein anabolic response following a nutrient stimulus or muscular contraction will be more pronounced in healthy young men than in young women. Specific aims: (1) To determine the magnitude of the acute response of skeletal muscle protein synthesis and net protein anabolism to a nutritional stimulus given before or after a bout of resistance exercise. (2) To determine the magnitude of the acute response of skeletal muscle protein synthesis and net protein anabolism to a nutritional stimulus providing an amount of energy that either matches or exceeds the exercise-induced energy expenditure. (3) To determine the differences between women and men in the response of skeletal muscle protein synthesis, efficiency of amino acid utilization for protein synthesis, leucine oxidation, and net protein anabolism to resistance exercise alone and in combination with a nutritional stimulus delivered before or after a bout of resistance exercise. Significance. These studies will provide insight into physiological mechanisms that regulate human muscle protein balance, and will be utilized as a basis from which to develop scientificallybased interventions for improving muscle protein balance in conditions such as aging, trauma, cancer, and AIDS.