Nyberg Michael, Jones Andrew M
Vascular Biology, Global Drug Discovery, Novo Nordisk A/S, Maaloev, Denmark.
Department of Sport and Health Sciences, University of Exeter, Exeter, United Kingdom.
Front Physiol. 2022 Jun 14;13:898395. doi: 10.3389/fphys.2022.898395. eCollection 2022.
Skeletal muscle is one of the most dynamic metabolic organs as evidenced by increases in metabolic rate of >150-fold from rest to maximal contractile activity. Because of limited intracellular stores of ATP, activation of metabolic pathways is required to maintain the necessary rates of ATP re-synthesis during sustained contractions. During the very early phase, phosphocreatine hydrolysis and anaerobic glycolysis prevails but as activity extends beyond ∼1 min, oxidative phosphorylation becomes the major ATP-generating pathway. Oxidative metabolism of macronutrients is highly dependent on the cardiovascular system to deliver O to the contracting muscle fibres, which is ensured through a tight coupling between skeletal muscle O utilization and O delivery. However, to what extent O delivery is ideal in terms of enabling optimal metabolic and contractile function is context-dependent and determined by a complex interaction of several regulatory systems. The first part of the review focuses on local and systemic mechanisms involved in the regulation of O delivery and how integration of these influences the matching of skeletal muscle O demand and O delivery. In the second part, alterations in cardiovascular function and structure associated with aging and heart failure, and how these impact metabolic and contractile function, will be addressed. Where applicable, the potential of exercise training to offset/reverse age- and disease-related cardiovascular declines will be highlighted in the context of skeletal muscle metabolic function. The review focuses on human data but also covers animal observations.
骨骼肌是最具活力的代谢器官之一，从静息状态到最大收缩活动时代谢率增加超过150倍就证明了这一点。由于细胞内ATP储备有限，在持续收缩过程中需要激活代谢途径以维持必要的ATP再合成速率。在最初阶段，磷酸肌酸水解和无氧糖酵解占主导，但随着活动持续超过约1分钟，氧化磷酸化成为主要的ATP生成途径。大量营养素的氧化代谢高度依赖心血管系统向收缩的肌纤维输送氧气，这通过骨骼肌氧气利用和氧气输送之间的紧密耦合得以确保。然而，就实现最佳代谢和收缩功能而言，氧气输送在何种程度上是理想的取决于具体情况，并由几个调节系统的复杂相互作用决定。综述的第一部分重点关注参与调节氧气输送的局部和全身机制，以及这些机制的整合如何影响骨骼肌氧气需求和氧气输送的匹配。在第二部分中，将探讨与衰老和心力衰竭相关的心血管功能和结构变化，以及这些变化如何影响代谢和收缩功能。在适用的情况下，将在骨骼肌代谢功能的背景下强调运动训练抵消/逆转与年龄和疾病相关的心血管功能下降的潜力。本综述侧重于人体数据，但也涵盖动物观察结果。
