Metabolic fuel selection: exercise and hypoxia

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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.**