Wolfe R R
University of Texas Medical Branch Galveston, Shriners Burns Institute Metabolism Unit 77550, USA.
Adv Exp Med Biol. 1998;441:147-56. doi: 10.1007/978-1-4899-1928-1_14.
Fatty acids are the most abundant source of endogenous energy substrate. They can be mobilized from peripheral adipose tissue and transported via the blood to active muscle. During higher intensity exercise, triglyceride within the muscle can also be hydrolyzed to release fatty acids for subsequent direct oxidation. Control of fatty acid oxidation in exercise can potentially occur via changes in availability, or via changes in the ability of the muscle to oxidize fatty acids. We have performed a series of experiments to distinguish the relative importance of these potential sites of control. The process of lipolysis normally provides free fatty acids (FFA) at a rate in excess of that required to supply resting energy requirements. At the start of low intensity exercise, lipolysis increases further, thereby providing sufficient FFA to provide energy substrates in excess of requirements. However, lipolysis does not increase further as exercise intensity increases, and fatty acid oxidation becomes approximately equal to the total amount of fatty acids available at 65% of VO2 max. When plasma FFA concentration is increased by lipid infusion during exercise at 85% VO2 max, fat oxidation is significantly increased. Taken together, these observations indicate that fatty acid availability can be a determinant of the rate of their oxidation during exercise. However, even when lipid is infused well in excess of requirements during high-intensity exercise, less than half the energy is derived from fat. This is because the muscle itself is a major site of control of the rate of fat oxidation during exercise. We have demonstrated that the mechanism of control of fatty acid oxidation in the muscle is the rate of entry into the mitochondria. We hypothesize that the rate of glycolysis is the predominant regulator of the rate of carbohydrate metabolism in muscle, and that a rapid rate of carbohydrate oxidation caused by mobilization of muscle glycogen during high intensity exercise inhibits fatty acid oxidation by limiting transport into the mitochondria. During low intensity exercise, glycogen breakdown and thus glycolysis is not markedly stimulated, so the increased availability of fatty acids allows their oxidation to serve as the predominant energy source. At higher intensity exercise, stimulation of glycogen breakdown and glycolysis cause increased pyruvate entry into the TCA cycle for oxidation, and as a consequence the inhibition of fatty acid oxidation by limiting their transport into the mitochondria.
脂肪酸是内源性能量底物最丰富的来源。它们可从外周脂肪组织中动员出来，并通过血液运输到活跃的肌肉。在高强度运动期间，肌肉内的甘油三酯也可被水解以释放脂肪酸用于随后的直接氧化。运动中脂肪酸氧化的控制可能通过可用性的变化，或通过肌肉氧化脂肪酸能力的变化来实现。我们进行了一系列实验，以区分这些潜在控制位点的相对重要性。脂解过程通常以超过供应静息能量需求所需的速率提供游离脂肪酸（FFA）。在低强度运动开始时，脂解进一步增加，从而提供足够的FFA以提供超过需求的能量底物。然而，随着运动强度增加，脂解不会进一步增加，并且脂肪酸氧化在最大摄氧量的65%时变得大约等于可用脂肪酸的总量。当在85%最大摄氧量的运动期间通过脂质输注增加血浆FFA浓度时，脂肪氧化显著增加。综上所述，这些观察结果表明，脂肪酸可用性可能是运动期间其氧化速率的一个决定因素。然而，即使在高强度运动期间脂质输注量远超需求时，仍不到一半的能量来自脂肪。这是因为肌肉本身是运动期间脂肪氧化速率的主要控制位点。我们已经证明，肌肉中脂肪酸氧化的控制机制是进入线粒体的速率。我们假设糖酵解速率是肌肉中碳水化合物代谢速率的主要调节因子，并且高强度运动期间肌肉糖原动员引起的快速碳水化合物氧化通过限制进入线粒体的转运来抑制脂肪酸氧化。在低强度运动期间，糖原分解以及因此的糖酵解不会受到明显刺激，所以脂肪酸可用性的增加使其氧化成为主要能量来源。在更高强度运动时，糖原分解和糖酵解的刺激导致丙酮酸进入三羧酸循环进行氧化增加，结果通过限制脂肪酸进入线粒体来抑制脂肪酸氧化。
