Plasticity and evolution of muscle metabolism

了解肌肉代谢的调节是有价值的，因为不同物种在受到环境和能量变化（压力）时，运动和调整肌肉功能的能力存在很大差异。我研究了调节脂肪（FAO）和碳水化合物氧化（CHO）的能力作为保存肌肉功能的重要机制。我的团队将解决几个关于肌肉代谢的问题：1)在组织、物种和应激反应中，决定FAO和CHO的关键调节因子是什么？2)是什么调控了缺氧时肌肉中有氧和无氧代谢的相互作用？3)动物如何应对多种应激源（寒冷和缺氧）？& 4)高原缺氧的真正代谢适应是什么？我们将主要关注代谢过程中决定线粒体氧化脂肪（肉碱棕榈酰基转移酶，CPTI）或碳水化合物（丙酮酸脱氢酶，PDH）能力的两个步骤。使用鳟鱼将使我们能够充分利用鱼类具有独立的快（白）和慢（红）肌肉块的事实，并且可能含有粮农组织所涉及的多种形式的重要蛋白质。我们将检查专门用于FAO的线粒体种群，并检查调节FAO的蛋白质的表达和功能。在小鼠中，我们的目标是确定正常和低氧条件下的运动燃料使用。我们还将探索几十年来的观察，CHO是首选和血液乳酸水平较低的慢性低氧。这可能涉及癌细胞在低氧条件下调节有氧和无氧代谢的途径。最后，我们正在研究秘鲁的一组小鼠物种，它们生活在不同的海拔高度，因此几代人都经历过低氧。这将使我们有机会在肌肉代谢水平上定义对低氧的真正适应。我们将通过展示保守和不同的调节FAO和CHO方法的替代模型，为脊椎动物肌肉重塑提供独特的见解。动物在低氧环境中生存的基于遗传的生理机制代表了适用于人类疾病的生物解决方案。

Understanding the regulation of muscle metabolism is valuable due to the wide diversity amongst species in ability to exercise & in adjusting their muscles to function when subjected to environmental & energetic changes (stress). I study the ability to regulate fat (FAO) & carbohydrate oxidation (CHO) as an important mechanism to conserve muscle function. My group will address several questions regarding muscle metabolism: 1) What are the key regulators that determine FAO & CHO between tissues, species & in response to stress? 2) What regulates the interaction between aerobic & anaerobic metabolism in muscles with hypoxia? 3) How do animals deal with multiple stressors (cold & hypoxia)? & 4) What are true metabolic adaptations to hypoxia at altitude? Mainly we will concentrate on 2 steps in metabolism that determine the ability of mitochondria to oxidize fat (carnitine palmitoyltransferase, CPTI) or carbohydrates (pyruvate dehydrogenase, PDH). Using trout will allow us to capitalize on the fact that fish have separate fast (white) & slow (red) muscle masses & may have multiple forms of important proteins involved in FAO. We will examine populations of mitochondria specializing in FAO & examine the expression & function of proteins that regulate FAO. In mice we aim to define exercise fuel use in normal & low oxygen conditions. We will also explore decades-old observations that CHO is preferred & blood lactate levels are lower in chronic low oxygen. This may involve a pathway shown in cancer cells to regulate aerobic & anaerobic metabolism in low oxygen. Finally, we are working with a group of mouse species in Peru that live at different altitudes & therefore experience low oxygen for generations. This will give us the opportunity to define a true adaptation to low oxygen at the level of muscle metabolism. We will provide unique insight into vertebrate muscle remodeling from alternate models demonstrating conserved & divergent methods of regulating FAO & CHO. Genetically-based physiological mechanisms used by animals to live in low oxygen environments represent biological solutions applicable to human disease.