The effects of beta-hydroxybutyrate on mitigating uric acid-induced changes in muscle cell mitochondrial bioenergetics

Abstract

Uric acid accumulates in the body in disease states and aggravates myriad pathologies, including joint pain, insulin resistance, and more. The mediating mechanisms of uric acid-induced disruption is via alterations in inflammatory status and direct effects on mitochondrial function, including disrupted respiration. Interestingly, the ketone beta-hydroxybutyrate (bHB) tends to have the opposite effects. In part, the relevance for this project is borne from the available evidence that indicates ketogenic diets tend to increase uric acid, while paradoxically improving metabolic outcomes, including mitochondrial function. Accordingly, the purpose of this work was to evaluate the competing effects of uric acid (UA) and bHB on mitochondrial bioenergetics in muscle cells. C2C12 muscle cells treated with UA (500 μM) tended to manifest reduced mitochondrial respiration across all conditions, particularly in a basal state (glutamate+malate), compared with control. In contrast, bHB (5mM) maintained respiration at normal levels throughout. The combination of bHB with UA increased respiration levels above UA alone, suggesting a protective effect. Future analyses will further phenotype the effects of these treatments on the production of reactive oxygen species and activation of inflammatory pathways. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.