High altitude is characterized by chronically low ambient temperatures and oxygen. To survive, highland native deer mice (Peromyscus maniculatus) are capable of high rates of prolonged thermogenesis due to elevated aerobic capacity (V̇O2max) in hypoxia. Deer mice primarily use fats to fuel their high metabolic rates for heat production. Carnitine palmitoyl-transferase 1 (CPT-1) is a rate-limiting step in mitochondrial fat oxidation, and a reduction in CPT-I sensitivity for its substrate L-carnitine is associated with a reduction in muscle fat use during high intensity exercise in mammals. Sensitivity of mitochondrial metabolism to ADP also changes with exercise. It is currently unknown whether similar mechanisms underpin regulation of fuel use during shivering, but I predicted that sensitivities to ADP and L-carnitine would be greater in highlanders than lowlanders and increase with acclimation. To address this question, I examined mitochondrial sensitivity to substrates involved in the fat oxidation pathway in low- and high- altitude deer mice born and raised in common laboratory conditions. Mice were also acclimated to high altitude condition of cold hypoxia to examine if the plasticity of these traits were affected by altitude ancestry. Consistent with previous findings, both high and lowland mice increased their cold-induced V̇O2max following cold hypoxia acclimation and rely primarily on lipids to fuel thermogenesis. High- and low-altitude deer mice responded differently to chronic cold hypoxia with highlanders showing a ~7-fold greater ADP sensitivity than lowlanders following acclimation. In contrast to the expected outcome, highlander deer mice tended to have a reduced sensitivity to L-carnitine compared to lowlanders that approached statistical significance. Neither sensitivity to palmitoylcarnitine sensitivity nor mitochondrial expression of FAT/CD36, thought to aid in mitochondrial fat delivery, showed differences between population or changes with acclimation, indicating that limitations to lipid oxidation during shivering likely occur at, or upstream of, CPT-I in the deer mouse. / Thesis / Master of Science (MSc) / Some animals can survive extremely harsh climates, such as high altitude. High altitude is characterized by unremitting cold and thin air, and these challenges can constrain aerobic activities in mammals. The North American deer mouse can thrive at high altitude by actively generating large amounts of body heat in a process known as thermogenesis. The deer mouse relies primarily on fats as fuel to support thermogenesis, but the cellular mechanisms that regulate the use of lipids to power thermogenesis remain unclear. To address this question, I induced shivering in deer mice from both high- and low-altitude populations that I exposed to simulated high- or low-altitude conditions. I then examined the effects of these treatments on the ability of shivering muscle to consume oxygen and fuel for thermogenesis. My thesis contributes to the current understanding of how mammals manage their energy supply to survive in a challenging environment.
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/29273 |
| Date | January 2023 |
| Creators | Baragar, Claire Eugenie |
| Contributors | McClelland, Grant B., Biology |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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