Multi-dimensional Roles of Ketone Bodies in Fuel Metabolism, Signaling, and Therapeutics

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283 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)262-284
Number of pages23
JournalCell Metabolism
Issue number2
StatePublished - Feb 7 2017

Bibliographical note

Funding Information:
The authors thank Peter Kannam for curating references, D. Andr? d'Avignon for performing NMR, Shannon E. Martin for performing total ketone body assay, Laura Kyro for graphics expertise, and the members of the P.A.C. lab, past and present, for their intellectual contributions to this review. P.A.C. is supported in part by NIH DK091538.


  • HMGCS2
  • SCOT
  • alternative fuel
  • cancer metabolism
  • carbohydrate restriction
  • cardiac metabolism
  • extrahepatic ketogenesis
  • fuel metabolism
  • ketogenic diet
  • mitochondrial function

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