Wright, DougCooper, Michael A2019-04-192019-04-192018-05-312018http://dissertations.umi.com/ku:15798https://hdl.handle.net/1808/27750Obesity and metabolic syndrome are a rising worldwide epidemic and have driven a subsequent increase in prediabetes and type 2 diabetes. We now know that patients who have prediabetes will begin to develop debilitating alterations in sensation due to early damage of peripheral sensory axons. There have been few therapies proposed to help patients developing metabolic syndrome induced painful neuropathies and those that have been developed often exhibit minimal benefit. While the mechanisms of prediabetes-induced peripheral neuropathy are still poorly understood, previous work has been able to show there is a significant benefit from physical activity that improve abnormal sensation and pain. Early studies in this work demonstrate that exercise alters the metabolic status of peripheral neurons and can normalize heightened mechanical sensitivity induced by a high fat diet. Utilizing a genetic rat model of differing intrinsic aerobic levels, our results show that genetic differences that result in varied metabolism alters peripheral nerve function and sensation. Highlighting the importance of metabolism, our studies show that exercise increases the utilization of fat based fuels, providing a novel mechanism for improved sensation. We performed studies in mice utilizing a ketogenic diet that is high in fat and low in carbohydrates to push fat utilization in nerves. These studies revealed that consumption of a ketogenic improved abnormal peripheral sensation. Contrary to exercise or a control diet, a ketogenic diet was able to prevent and also reverse high fat diet induced mechanical allodynia. In addition to improved sensation, a ketogenic diet increased axonal growth in vitro and in vivo. This exciting result of improved nerve growth has the potential to benefit millions of patients worldwide experiencing neuropathy and pain due to axonal degeneration.226 pagesenCopyright held by the author.NeurosciencesExerciseHigh-Fat DietKetogenic DietMetabolismPainPeripheral NervesDissertationhttps://orcid.org/0000-0002-9312-0399openAccess