Multi-dimensional Roles of Ketone Bodies in Fuel Metabolism, Signaling, and Therapeutics.
Ketone body metabolism is a central node in physiological homeostasis. In this review, we discuss how ketones serve discrete fine-tuning metabolic roles that optimize organ and organism performance in varying nutrient states and protect from inflammation and injury in multiple organ systems. Traditionally viewed as metabolic substrates enlisted only in carbohydrate restriction, observations underscore the importance of ketone bodies as vital metabolic and signaling mediators when carbohydrates are abundant. Complementing a repertoire of known therapeutic options for diseases of the nervous system, prospective roles for ketone bodies in cancer have arisen, as have intriguing protective roles in heart and liver, opening therapeutic options in obesity-related and cardiovascular disease. Controversies in ketone metabolism and signaling are discussed to reconcile classical dogma with contemporary observations.
Center for Metabolic Origins of Disease, Sanford Burnham Prebys Medical Discovery Institute, Orlando, FL 32827, USA.
Patrycja
P
Puchalska
Center for Metabolic Origins of Disease, Sanford Burnham Prebys Medical Discovery Institute, Orlando, FL 32827, USA. Electronic address: pcrawford@sbpdiscovery.org.
Peter A
PA
Crawford
D000818:Animals; D004734:Energy Metabolism; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D007657:Ketone Bodies / Q000378:metabolism* / Q000627:therapeutic use*; D009369:Neoplasms / Q000378:metabolism; D000066829:Neuroprotection; D015398:Signal Transduction
D007657:Ketone Bodies
HMGCS2; NAFLD; SCOT; alternative fuel; cancer metabolism; carbohydrate restriction; cardiac metabolism; extrahepatic ketogenesis; fuel metabolism; ketogenic diet; mitochondrial function