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: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=668308
• 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变暖的气候中生存的能力，这种气候促进了环境缺氧（低氧可用性）。至关重要的是要弄清楚缺氧敏感的鲑鱼如何或是否会管理它们的能量储备来科普缺氧并继续进行完成产卵迁徙所需的运动。第一个项目将研究虹鳟鱼（野生鲑鱼的近亲）在缺氧和分级游泳过程中如何调节代谢燃料（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。控制脂解速率（脂质动员）和葡萄糖产生（碳水化合物动员）变化的主要激素信号将被表征。在缺氧期间或在游泳隧道中运动期间，将在静态呼吸计中休息的插管动物中使用代谢示踪剂测量储存部位（脂肪组织和肝脏）的燃料释放速率。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关键作用。不幸的是，代谢燃料供应的调节和膜结构的变化之间的功能联系还不清楚。在第二个项目中，将使用耐缺氧的金鱼和缺氧敏感的鳟鱼，并进行比较，以量化适应低氧和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调节其膜的脂肪酸组成和胆固醇含量，以应对慢性缺氧和温度，以及这些环境压力如何影响乳酸（MCT），葡萄糖（GLUT）和脂肪酸（FAT/CD 36）的跨膜转运蛋白的基因表达，蛋白质丰度和活性。利用鱼类、昆虫和哺乳动物的膜，我们还将开发一种改进版的“新陈代谢的膜起搏器理论”，该理论现在将纳入胆固醇水平和脂肪酸组成的变化。这个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得到极大的提高。全球变暖和随之而来的缺氧对生活在水中的“冷血”动物（=外温动物）造成了重大的生理挑战。拟议中的实验涉及一个基本的研究问题：[鱼类可以利用什么样的生理机制来科普环境中的高温和缺氧]，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]。外温动物科普未来变暖的能力可能主要取决于保护膜功能，以防止其新陈代谢受到致命的破坏。