Plasticity and evolution of muscle metabolism

了解肌肉代谢的调节是有价值的，因为物种之间在运动能力和调整肌肉功能时受到环境和能量变化（压力）的广泛多样性。我研究调节脂肪（FAO）和碳水化合物氧化（CHO）的能力，作为保护肌肉功能的重要机制。 我的小组将解决关于肌肉代谢的几个问题：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)什么调节肌肉缺氧时有氧和无氧代谢之间的相互作用？3)动物如何应对多重压力（寒冷和缺氧）？&4）什么是真正的代谢适应高原缺氧？ 我们将主要集中在代谢中的两个步骤，决定线粒体氧化脂肪（肉毒碱棕榈酰转移酶，CPTI）或碳水化合物（丙酮酸脱氢酶，PDH）的能力。 使用鳟鱼将使我们能够利用这样一个事实，即鱼有单独的快速（白色）和缓慢（红色）肌肉质量，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FAO的线粒体群体，并研究调节FAO的蛋白质的表达和功能。 在小鼠中，我们的目标是定义在正常和低氧条件下的运动燃料使用。我们还将探讨数十年来的观察结果，即CHO是首选的，慢性低氧下的血乳酸水平较低。 这可能涉及癌细胞中显示的调节低氧下有氧和无氧代谢的途径。 最后，我们正在研究秘鲁的一组老鼠物种，它们生活在不同的海拔高度，因此几代人都要经历低氧环境。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。我们将提供独特的见解脊椎动物肌肉重塑从替代模型展示保守和不同的方法调节粮农组织和CHO。动物在低氧环境中生活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.