Thermal influences governing oxygen delivery and extraction on skeletal muscle metabolism during exercise

人体暴露于寒冷和炎热的环境会影响向骨骼肌输送氧气（O2）和线粒体氧化磷酸化（OXPHOS）能力。冷热暴露对骨骼肌O2输送和线粒体O2提取的波动控制着能量代谢的调节机制。能量代谢是多因素的，受运动和环境的调节。虽然已知在冷和热环境下运动分别增加脂质和碳水化合物氧化，但仍然存在两个问题：1)运动和环境代谢主要是单独研究，对综合影响的见解有限；2)在运动研究中，冷和热对O2可用性和提取的影响尚未得到全面评估，随后与能量代谢联系起来。运动过程中极端环境下骨骼肌O2输送和线粒体O2提取的改变及其对骨骼肌能量代谢代谢转变的影响尚不清楚。我的研究项目旨在研究在寒冷和炎热的运动过程中对氧气输送和提取的热影响，并随后确定它们在调节骨骼肌代谢中的作用。在接下来的几年里，将进行一系列研究，通过空间分辨光谱技术研究骨骼肌组织的氧合和摄氧量，通过高分辨率呼吸测量法研究体外线粒体OXPHOS能力，以及在寒冷和炎热的运动中通过肌肉活检研究全身和肌肉内能量底物的利用。我的项目第一阶段将包括专门针对冷热环境下运动时氧气输送和提取波动的研究。第二阶段将重点研究基于第一阶段结果的能量代谢调节机制。该研究项目旨在提高我们对人体生物系统的认识，更准确地说，是我们对热应激下肌肉热生理和氧化生理以及能量代谢的理解。除此之外，我们还旨在为普通民众实施信息丰富的环境运动指南，并为职业工人/军事人员/户外运动运动员制定安全工作指南和协议，这些工人/军事人员/户外运动运动员必须在寒冷或温暖的条件下进行体力劳动，有时是关键任务。这项工作的结果将进一步用作工业和技术发展的基准，以限制低温和高温对地下矿工、消防员、食品加工工人、建筑工人和其他职业群体的有害影响。

Human exposure to cold and hot environments influences oxygen (O2) delivery to skeletal muscles and mitochondrial oxidative phosphorylation (OXPHOS) capacity. Fluctuations in O2 delivery to skeletal muscles and O2 extraction in the mitochondria from cold or heat exposure govern mechanisms regulating energy metabolism. Energy metabolism is multi-factorial and modulated by exercise and the environment. While it is known that exercise in a cold and hot environment increases lipids carbohydrates oxidation, respectively, two problems remain: 1) exercise and environmental metabolism have been primarily studied independently with limited insights on combined influences, and 2) the effects of cold and heat on O2 availability and extraction has yet to be comprehensively evaluated during exercise studies, and subsequently linked to energy metabolism. The combined influence of altered O2 delivery to skeletal muscles and O2 extraction in mitochondria and their influence on the metabolic shift in skeletal muscle energy metabolism in extreme environments during exercise is unclear. My research program aims at examining the thermal influences governing O2 delivery and extraction during exercise in the cold and heat, and subsequently determine their roles in regulating skeletal muscle metabolism. Over the next years, a series of studies will be conducted to investigate skeletal muscle tissue oxygenation and oxygen uptake via spatially-resolved spectroscopy technology, in vitro mitochondrial OXPHOS capacity via high resolution respirometry, as well as systemic and intra-muscular energy substrate utilization from muscle biopsies during exercise in the cold and heat. Phase I of my program will included studies specifically targeting fluctuations in O2 delivery and extraction studies during exercise in cold and hot environment. Phase II will focus on studies examining energy metabolism regulating mechanisms based on results of Phase I. This research program is designed to improve our knowledge of human biological systems, more precisely, our understanding of muscle thermal and oxidative physiology and energy metabolism under thermal stress. Beyond this scope, we also aim to implement informative environmentally-based exercise guidelines for the general population in addition to develop safety working guidelines and protocols for occupational workers/military personnel/outdoor sports athletes having to perform physical, sometimes critical tasks under cold or warm conditions. The results stemming from this work will further be used as a benchmark in industrial and technological development to limit the detrimental influences of cold and heat for underground miners, firefighters, food processing workers, construction workers, and other occupational groups.