Metabolic fuel selection: exercise and hypoxia

代谢燃料选择：运动和缺氧

• 批准号: RGPIN-2017-05955
• 负责人: Weber, JeanMichel
• 金额: $ 2.84万
• 依托单位: University of Ottawa
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=630836
• 关键词: Metabolic; fuel; selection; exercise; hypoxia

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.

这项研究涉及鱼类在促进环境缺氧（低氧可用性）的变暖气候中生存的能力。找出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，并继续进行完成产卵迁徙所需的运动，这是至关重要的。第一个项目将研究虹鳟鱼（野生鲑鱼的近亲）在缺氧和分级游泳期间如何调节代谢燃料（脂质和碳水化合物）的动员，以及这种调节如何受到温度的影响。控制脂肪分解速率（脂质动员）和葡萄糖生成（碳水化合物动员）变化的主要激素信号将被表征。燃料从储存部位（脂肪组织和肝脏）释放的速率将用代谢示踪剂测量，在缺氧或在游泳隧道中锻炼时，在静息呼吸计中放置导管的动物。生物膜描绘了细胞和它们所包含的细胞器。因此，膜在调节细胞、组织和身体隔室之间的燃料运动中起着关键作用。不幸的是，代谢燃料供应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，将使用耐缺氧的金鱼和对缺氧敏感的鳟鱼进行比较，以量化适应低氧和低温度对膜组成和允许跨膜运输燃料的蛋白质的影响。这项工作将确定鱼类如何在慢性缺氧和温度下调节其膜的脂肪酸组成和胆固醇含量，以及这些环境应激如何影响基因表达、蛋白质丰度和乳酸（MCT）、葡萄糖（GLUT）和脂肪酸（FAT/CD36）跨膜转运蛋白的活性。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版的“代谢膜起搏器理论”，现在将胆固醇水平和脂肪酸组成的变化纳入其中。这个理论的新版本预测膜结构如何影响动物代谢能力的能力应该大大提高。全球变暖和随之而来的缺氧给生活在水中的“冷血”动物（=变温动物）带来了重大的生理挑战。拟议中的实验处理了一个基本的研究问题：[鱼类可以利用什么样的生理机制来应对环境的高温和缺氧]，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]。变温动物应对未来变暖的能力可能在很大程度上取决于保护膜功能，以防止新陈代谢受到致命的破坏。