Plasticity and evolution of muscle metabolism

了解肌肉新陈代谢的调节是有价值的，因为不同物种在锻炼能力上存在很大差异，即在受到环境和能量变化(压力)的影响时，调整他们的肌肉以适应功能。我研究了脂肪调节能力(FAO)和碳水化合物氧化(CHO)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)决定FAO和CHO在组织、物种和应激反应中的关键调节因素是什么？2)什么调节缺氧肌肉中有氧和无氧代谢之间的相互作用？3)动物如何应对多重应激(寒冷和缺氧)？和4)什么是真正的代谢适应高原低氧？我们将主要集中在决定线粒体氧化脂肪(肉碱棕榈酰转移酶，CPTI)或碳水化合物(丙酮酸脱氢酶，PDH)能力的代谢的两个步骤。使用鲑鱼将使我们能够利用这样一个事实，即鱼有不同的快(白)和慢(红)肌肉块，可能有多种形式的重要蛋白质参与粮农组织。我们将研究专门研究粮农组织的线粒体群体，并研究调节粮农组织的蛋白质的表达和功能。在小鼠身上，我们的目标是确定运动燃料在正常和低氧条件下的使用。我们还将探索几十年来的观察结果，即CHO是首选的&慢性低氧时血乳酸水平较低。这可能涉及到癌细胞在低氧条件下调节有氧和无氧代谢的途径。最后，我们正在与秘鲁的一组老鼠进行合作，这些老鼠生活在不同的海拔地区，因此世代都经历着低氧。这将使我们有机会在肌肉新陈代谢水平上定义对低氧的真正适应。我们将从不同的模型中提供对脊椎动物肌肉重塑的独特见解，展示保守的和不同的调控FAO和CHO的方法。动物生活在低氧环境中所使用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.