Human skeletal muscle thermogenesis and plasticity in response to various environmental conditions

作为恒温动物，人类面临着在不同环境条件下通过代谢产热（产热）保持体温升高和恒定的重要挑战。骨骼肌是这种产热的主要来源，然而，尽管它们对寒冷生存和表现相对重要，但调节和促进这些产热过程的机制仍然知之甚少。我的研究计划的长期目标是阐明在人类暴露于寒冷的骨骼肌中调节产热过程的机制。为了实现这一目标，研究人员将对男性和女性进行单次或多次低温暴露，目的是了解：1)在人体精心控制的低温暴露过程中，皮肤和内脏中发现的温度传感器的刺激如何对骨骼肌产热产生不同的调节；2)急性和慢性冷暴露时肌肉产热的相对贡献，负责这种肌肉产热的代谢过程和用于为其提供燃料的能量底物；3)反复寒冷暴露或运动训练导致的骨骼肌代谢变化是否能对两种类型的肌肉需求产生普遍的益处。通过将传统的测量方法与新颖的分子成像方法相结合，该研究将建立在肌肉活检的局部视图的基础上，以非侵入性地提供静止和刺激条件下新颖和创新的实时全肌肉特异性代谢。加深对肌肉产热的理解是一种重要的手段：1)提高运动表现；2)了解其在不同热条件下对运动和精细运动的影响；3)了解刺激温度传感器对产热代谢过程激活的影响。该研究还填补了对各种环境条件下体温调节和代谢反应的性别差异的巨大知识空白。这对人体热平衡的生物物理模型的发展具有重大的转化意义。这必然会影响室内气候法规和商业和住宅建筑的能源消耗，以及预测加拿大武装部队和一般劳动力的人员生理准备和表现。

As endotherms, humans face the vital challenge of maintaining an elevated and constant body temperature under varying environmental conditions, through the metabolic production of heat (thermogenesis). Skeletal muscles are the predominant source of this heat production, however, despite their relative importance for cold survival and performance, the mechanisms that regulate and fuel these heat-producing processes remain poorly understood. The long-term goal of my research program is to elucidate the mechanisms that regulate the heat-producing processes in skeletal muscle of humans exposed to the cold. To accomplish this goal, men and women will be exposed to a single or repeated cold exposure with the aim of understanding: 1) how the stimulation of temperature sensors found in the skin and within internal organs may differentially regulate skeletal muscle thermogenesis during carefully controlled cold exposure in humans; 2) the relative contribution of muscle thermogenesis during acute and chronic cold exposure, the metabolic processes responsible for this muscle thermogenesis and the energy substrates used to fuel them and; 3) whether changes in skeletal muscle metabolism resulting from either repeated cold exposure or exercise training can confer generalized benefits across both types of muscle demands. By combining traditional measurements with novel molecular imaging modalities, the proposed research will build upon the localized view derived from muscle biopsies to non-invasively providing novel and innovative real-time whole muscle-specific metabolism under resting and stimulated conditions. Building a greater depth of understanding in muscle thermogenesis is significant as a means of: 1) improving athletic performance; 2) understanding its impact on locomotion and fine motor movement under various thermal conditions and; 3) understanding the impact of stimulating temperature sensors on the activation of heat-producing metabolic processes. The proposed research also fills the large knowledge gap in the sex-disparities in thermoregulatory and metabolic responses to various environmental conditions. This has dramatic translational implications in the development of biophysical models of human thermal balance. This invariably impacts indoor climate regulations and the energy consumption of commercial and residential buildings, as well as predicting personnel physiological readiness and performance in Canadian Armed Forces and the general labour force.