Exercise Substrate Utilization:The Crossover Concept

描述（由申请人提供）：我们的总体目标是确定和了解在持续的、亚极限运动中控制内源性碳水化合物、脂质和氨基酸来源的能量平衡的因素。一个相关的目标是了解不同的生活状况（身体健康、饮食、性别、年龄）如何影响人类对底物利用的平衡（分配）。我们方法的理论基础是“交叉概念”，它假设在吸收后状态的休息和轻度到中等强度的运动期间，脂质为肌肉和整个身体提供了最大比例的能量。然而，随着运动强度从中等到艰苦再到最大，工作肌肉中底物利用的平衡会从脂质过渡到碳水化合物。利用这一概念，我们试图描述运动、运动训练、卵巢类固醇、年龄和饮食史影响底物利用平衡的机制。为了实现我们的总体目标，我们建议探讨两个具体目标。这些是：(1)描述运动强度和耐力训练对肌肉和全身脂肪酸氧化的相互作用；(2)评价年龄和卵巢性类固醇对底物利用平衡的影响。有了这些数据，我们将能够扩展我们的基质利用模型。为了评估运动强度的影响，并对耐力训练前后给定的相对和绝对运动强度进行比较，Aim 1年轻男性将在训练前以功率输出（P0）达到45%和65% vo2峰值时进行研究；训练后分别在训练前产生65%V02峰值的P0和新的65%V02峰值进行研究。为了评估全身和工作肌肉（腿）水平的急性和长期代谢和酶反应，我们将结合使用示踪剂{[1- 13c]棕榈酸酯，[1,1,2,3,3- 2h2]-甘油（d5 -甘油）和d2 -葡萄糖}，间接量热法，（a-v）测量，活检，以及可能的核磁共振波谱。对于老年男性、年轻闭经者以及老年绝经后女性的Aim 2研究，我们将使用示踪剂{[1-13C]棕榈酸酯、d5 -甘油、D2-和[1-13C]葡萄糖，以及[1-13C]亮氨酸}，并使用间接量热法。在老年妇女中，将采用纵向设计来评估训练和HRT对基底分配的影响。年龄匹配的男性也将被研究。所有的技术，无论是涉及运动生理学、间接量热法、示踪剂输注和血液取样、代谢物衍生化、GC /MS同位素富集测定、代谢物和激素测定、Western blotting和饮食控制，都是调查组高度发展的。此外，我们有辅助人员和设施进行纵向培训研究

DESCRIPTION (provided by applicant): Our overall objective is to identify and understand the factors that control the balance of energy derived from endogenous carbohydrate, lipid, and amino acid sources during sustained, submaximal exercise. A related objective is to understand how various life situations (physical fitness, diet, gender, age) affect the balance of substrate utilization (partitioning) in humans. The theoretical basis of our approach is the 'Crossover Concept' which postulates that during rest and mild to moderate intensity exercise in the post-absorptive state, lipids provide the greatest proportion of energy for muscle and the body at large. However, as the exercise intensity increases from moderate to hard to maximal, the balance of substrate utilization in working muscle switches, or 'crosses over' from lipid to carbohydrate. Using this concept, we seek to describe the mechanisms by which exercise, exercise training, ovarian steroids, age, and dietary history affect the balance of substrate utilization. In pursuit of our overall objective, we propose to explore two specific aims. These are to: (1) describe the interactive effects of exercise intensity and endurance training on muscle and whole body fatty acid oxidation; and (2) evaluate the effects of aging and ovarian sex steroids on the balance of substrate utilization. With these data we shall be able to expand our model of substrate utilization. To assess effects of exercise intensity and to make comparisons at given relative and absolute exercise intensities before and after endurance training, for Aim 1 young men will be studied before training at power outputs (P0) that elicit 45 and 65% VO2peak; after training they will be studied at the P0 that elicited 65%V02peak before training, and at the new 65%V02 peak. To assess acute and long-term metabolic and enzymatic responses at whole-body and working muscle (leg) levels we will use the combination of tracers {[1-13C]palmitate, [1,1,2,3,3-2H2]-glycerol (D5-glycerol), and D2-glucose}, indirect calorimetry, (a-v) measurements, biopsies, and, possibly, NMR spectroscopy. For Aim 2 studies on older men, young amenorrhic as well as older postmenopausal women we will use tracers {[1-13C]palmitate, D5-glycerol, D2- and [1-13C]glucose, as well as [1-13C]leucine}, and indirect calorimetry. On older women longitudinal designs will be employed to assess effects of training and HRT on substrate partitioning. Age-matched males will also be studied. All techniques, whether they involve exercise physiology, indirect calorimetry, tracer infusion and blood sampling, metabolite derivatization, isotopic enrichment determination by GC /MS, metabolite and hormone assays, Western blotting and dietary control, are highly developed by the investigative team. Further, we have the auxiliary personnel and facilities to conduct longitudinal training studies