Lutsiv, Tymofiy, authorThompson, Henry J., advisorWilusz, Carol, committee memberFoster, Michelle T., committee member2019-01-072019-01-072018https://hdl.handle.net/10217/193091Physical inactivity is one of the risk factors for developing breast cancer. Aerobic capacity is an objective measure of an individual's activity behavior as physical exercise improves their ability to consume, transfer, and utilize oxygen. Variability in responses to the same physical exercise program led scientists to determine that there are two components of aerobic capacity—inducible and inherent. The latter became possible to study when two models with high (HIAC) and low (LIAC) inherent aerobic capacity were created. A number of studies conducted on these models showed that not only do these strains differ in their exercise performance but also in their susceptibility to disease. LIAC animals gain more weight and exhibit reduced fatty acid oxidation compared with their HIAC counterparts, especially on a high-fat diet. Based on these observations, my working hypothesis is that inherent aerobic capacity underlies an individual's metabolic flexibility. Metabolically inflexible cells exhibit increased glucose utilization, anabolic metabolism, as well as cell proliferation and survival. Interestingly, similar factors are also associated with carcinogenesis. HIAC animals appear to be metabolically more flexible on a systemic and cellular level than their LIAC counterparts. Additionally, our laboratory previously showed that LIAC animals exhibited greater incidence, multiplicity, and lower latency of breast tumors than HIAC upon carcinogen administration. To reveal the underlying mechanisms of their different carcinogenic responses, we analyze protein expression patterns in the mammary gland and tumors of HIAC/LIAC models. We demonstrate that LIAC animals upregulate pathways associated with glucose utilization, protein and fatty acid synthesis, as well as other carcinogenic signatures, whereas HIACs are associated with energy sensing, fatty acid oxidation, and cell cycle arrest. Consequently, we propose that higher inherent aerobic capacity renders cells metabolically more flexible and reduces their susceptibility to breast cancer development.born digitalmasters thesesengCopyright and other restrictions may apply. User is responsible for compliance with all applicable laws. For information about copyright law, please see https://libguides.colostate.edu/copyright.inherent aerobic capacitymetabolic flexibilityintracellular signalingbreast cancerText