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Concluding Remarks and Future Perspectives
Ketone bodies are emerging as crucial regulators of metabolic health. More than just a metabolite, the ketone body βOHB can regulate cellular processes directly via HDAC inhibition and binding to cell surface receptors, and indirectly by altering the levels of other regulatory metabolites including acetyl-CoA, succinyl-CoA, and NAD+. The ability of βOHB to regulate HDAC activity and thereby epigenetic gene regulation is particularly notable for potentially implicating a wide variety of genes as regulatory targets of βOHB. βOHB is already known to induce resistance to oxidative stress via HDAC inhibition, and other HDAC inhibitors regulate gluconeogenesis. The unique effects of βOHB may help explain the therapeutic benefit of low-carbohydrate and ketogenic diets. However, teasing apart the specific role of βOHB in the effects of a ketogenic diet is a challenging task. Ketogenic diets inextricable combine reduced carbohydrate consumption, reduced glucose utilization, reliance on beta-oxidation of lipids for energy, reduced insulin signaling, and increased glucagon signaling, along with increased ketone body levels . New experimental tools are required to permit the safe manipulation of βOHB levels outside of the confines of a ketogenic diet in order to understand the full spectrum of action of βOHB in amelioration of metabolic disease.