Metabolic fuel selection: exercise and hypoxia

这项研究涉及鱼类在促进环境缺氧(低氧气供应)的气候变暖中生存的能力。关键是要找出对缺氧敏感的鲑鱼如何或是否会管理它们的能量储备来应对缺氧，并继续进行完成它们产卵迁移所需的运动。第一个项目将研究彩虹鲑鱼(野生鲑鱼的近亲)在低氧和分级游泳时如何调节代谢燃料(脂肪和碳水化合物)的动员，以及这种调节如何受到温度的影响。主要的激素信号控制脂肪分解速率(脂肪动员)和葡萄糖产生(碳水化合物动员)的变化将被描述。储存部位(脂肪组织和肝脏)的燃料释放速率将用新陈代谢示踪剂测量，这些动物在缺氧或在游泳隧道中锻炼时，在静态呼吸仪中休息。生物膜描绘细胞及其所包含的细胞器。因此，膜在调节细胞、组织和身体隔间之间的燃料运动方面起着关键作用。不幸的是，代谢燃料供应的调节和膜结构变化之间的功能联系尚不清楚。在第二个项目中，将使用耐低氧的金鱼和对低氧敏感的鲑鱼进行比较，以量化适应低氧和温度对膜组成和允许燃料跨膜运输的蛋白质的影响。这项工作将确定鱼类如何调节其细胞膜的脂肪酸组成和胆固醇含量以响应慢性低氧和温度，以及这些环境应激如何影响乳酸(MCT)、葡萄糖(GLUT)和脂肪酸(FAT/CD36)的跨膜转运体的基因表达、蛋白质丰度和活性。利用鱼类、昆虫和哺乳动物的细胞膜，我们还将开发一种改进的“新陈代谢膜起搏器理论”，现在将纳入胆固醇水平和脂肪酸组成的变化。这一新版本的理论预测膜结构如何影响动物代谢能力的能力应该会大大提高。全球变暖和随之而来的低氧给生活在水中的冷血动物带来了重大的生理挑战。拟议中的实验涉及一个基本的研究问题：[鱼类可以利用什么生理机制来应对环境高温和缺氧]，但它们也将有助于解决一个重要的应用问题[野生鲑鱼种群的长期保护]。外温体应对未来变暖的能力可能关键取决于保护膜功能，以防止其新陈代谢受到致命破坏。

This research deals with the ability of fish to survive in a warming climate that promotes environmental hypoxia (low oxygen availability). It is essential to find out how or whether hypoxia-sensitive salmonids will manage their energy reserves to cope with hypoxia and to keep performing the exercise needed to complete their spawning migrations. The first project will investigate how rainbow trout (a close relative of wild salmon) regulate the mobilization of metabolic fuels (lipids and carbohydrates) during hypoxia and graded swimming, as well as how this regulation is affected by temperature. The main hormonal signals controlling changes in lipolytic rate (lipid mobilization) and glucose production (carbohydrate mobilization) will be characterized. Rates of fuel release from storage sites (adipose tissue and liver) will be measured with metabolic tracers in catheterized animals resting in a static respirometer during hypoxia or exercising in a swim tunnel. Biological membranes delineate cells and the organelles that they contain. Therefore, membranes play a key role in modulating fuel movements between cells, tissues, and body compartments. Unfortunately, the functional links between the regulation of metabolic fuel supply and changes in membrane structure are not understood. In the second project, hypoxia-tolerant goldfish and hypoxia-sensitive trout will be used and compared to quantify the effects of acclimation to low oxygen and to temperature on membrane composition and on the proteins that allow transmembrane transport of fuels. This work will determine how fish modulate the fatty acid composition and cholesterol content of their membranes in response to chronic hypoxia and temperature, and how these environmental stresses affect the gene expression, protein abundance, and activity of transmembrane transporters for lactate (MCT), glucose (GLUT) and fatty acids (FAT/CD36). Using membranes from fish, insects and mammals, we will also develop an improved version of “the membrane pacemaker theory of metabolism” that will now incorporate changes in cholesterol levels as well as in fatty acid composition. The power of this new version of the theory to predict how membrane structure affects the metabolic capacity of animals should be greatly improved. Global warming and subsequent hypoxia create a major physiological challenge for “cold-blooded” animals (=ectotherms) living in water. The proposed experiments deal with a fundamental research question: [what battery of physiological mechanisms can fish harness to cope with environmental heat and hypoxia], but they will also help to solve an important applied problem [the long-term conservation of wild salmon populations]. The capacity of ectotherms to cope with a warmer future could critically depend on protecting membrane function to prevent a fatal disruption of their metabolism.**