Studies of Interaction Effects between Ketone Metabolism and Mitochondrial Function and Biogenesis

Ketogenic diets or very-low-carbohydrate diets are characterized by a reduction in carbohydrates and a relative increase in the proportions of protein and especially fat. The diets have been successfully used in the treatment of epilepsy since early 1920s. Ketone bodies generated by fatty acid oxidation from the ketogenic diet, which mimics the metabolic state of starvation, forcing the body to utilize this alternative metabolites for its primary source of energy. The energy metabolism involves pyruvate oxidation, fatty acids beta-oxidation, the citric acid cycle, oxidative phosphorylation, and also ketogenesis and ketolysis are all processed in the mitochondria. During recent years, an increasing amount of diet intervention in other disease has been reported. Despite all the benefits ketones and popular with the masses, it is important to note that the above normal elevation level of ketones in the circulation may tend to interfere with normal cellular functioning or further to illicit various pathological complications. Therefore, there is need to identify the potential risk of long term ketone metabolism.To estimate the interaction between ketone metabolism and mitochondrial function and also the effects of mitochondrial function and biogenesis under long term above normal concentration of ketone bodies will be study in this plan. This plan includes cell models and animal model to evaluate the proposal. Importantly, the study of long term elevated level of ketone bodies in the animal will provide insight into the potential progression of disease complications. Completion of this study will provide information to better understand the potential roles of ketone bodies in energy metabolism and long term effects on development of pathological complications and also provide possible preventive and therapeutic strategy.