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Access Type
WSU Access
Date of Award
January 2023
Degree Type
Dissertation
Degree Name
Ph.D.
Department
Physiology
First Advisor
Robert Wessells
Abstract
Exercise has many beneficial effects on human health. However, certain life circumstancescan prevent individuals from exercising and their health may suffer as a result. A better understanding of the genetic and molecular mediators of exercise performance and adaptations can lead to the development of therapeutics, which could improve the health of compromised or diseased populations. In a collaborative effort, we identified Iditarod (CG33143) as the Drosophila homolog of mammalian FNDC5/Irisin. FNDC5/Irisin is known to mediate some of the endocrine effects of exercise but its role on exercise performance and exercise-induced cardiac autophagy has not been studied. Muscle-specific knockdown of Iditarod significantly reduced endurance and blunted the adaptive response to exercise training. Conversely, muscle-specific overexpression of Iditarod increased endurance and conferred adaptations in unexercised flies. Chronic exercise training upregulated cardiac Atg8 staining in wild-type animals but Iditarod mutant flies gain no such benefit. We also investigated the interaction of Iditarod with octopamine, Sestrin, and spargel. We found that octopamine feeding or muscle-specific overexpression of Sestrin or spargel increased Iditarod mRNA. Iditarod was required for the beneficial effects of octopamine feeding on exercise adapations, but Iditarod was not required for the beneficial effects of Sestrin or spargel in the exercise response. These results indicate that Iditarod is a conserved exercise gene. Furthermore, we identified novel effects of Iditarod on exercise performance and interactions with other exercise molecules. Lastly, we tested the role of Iditarod in the cold stress response of Drosophila because FNDC5/Irisin increases non-shivering thermogenesis in mammals during cold stress. We found that Iditarod is required in muscle for normal response to cold stress. In conclusion, we have identified that Iditarod is homologous to mammalian FNDC5/Irisin and it has conserved roles in exercise and cold stress.
Recommended Citation
Cobb, Tyler, "Iditarod, Homolog Of Fndc5/irisin, Is A Novel Regulator Of Exercise Performance And Cold Stress In Drosophila" (2023). Wayne State University Dissertations. 3792.
https://digitalcommons.wayne.edu/oa_dissertations/3792