UCLA

Exercise is an effective means of preventing and treating metabolic disorders such as insulin resistance. The mechanism by which exercise prevents complex diseases, however, is not well understood. Mitochondria are intracellular organelles intimately linked with metabolic disorders. Mitochondria are unique in that they possess their own, albeit incomplete, genetic material termed mitochondrial DNA (mtDNA). The primary objectives of this thesis were to: (1) determine the impact of voluntary aerobic exercise upon mtDNA in various metabolic organs and (2) elucidate the possible mechanism(s) by which exercise influences mtDNA. To determine mitochondrial abundance, mtDNA is used as a surrogate readout. We subjected female mice from the Hybrid Mouse Diversity Panel (HMDP) to two separate lifestyles, with or without voluntary aerobic exercise. In skeletal muscle and liver, exercised animals showed a significant increase in mtDNA content compared to the unexercised sedentary group. Average running speed was positively correlated with mtDNA content in skeletal muscle. Candidate genes that may be involved in the increased mtDNA content have also been identified. Future research should focus on thorough in-depth studies examining the genes involved in the mechanism(s) by which this increase occurs and if such increase confer the health benefits associated with exercise such as reductions in liver fats using genome-wide association studies.