Ketone body metabolism and cardiovascular disease

David G. Cotter, Rebecca C. Schugar, Peter A. Crawford

Research output: Contribution to journalReview article

158 Scopus citations

Abstract

Ketone bodies are metabolized through evolutionarily conserved pathways that support bioenergetic homeostasis, particularly in brain, heart, and skeletal muscle when carbohydrates are in short supply. The metabolism of ketone bodies interfaces with the tricarboxylic acid cycle, β-oxidation of fatty acids, de novo lipogenesis, sterol biosynthesis, glucose metabolism, the mitochondrial electron transport chain, hormonal signaling, intracellular signal transduction pathways, and the microbiome. Here we review the mechanisms through which ketone bodies are metabolized and how their signals are transmitted. We focus on the roles this metabolic pathway may play in cardiovascular disease states, the bioenergetic benefits of myocardial ketone body oxidation, and prospective interactions among ketone body metabolism, obesity, metabolic syndrome, and atherosclerosis. Ketone body metabolism is noninvasively quantifiable in humans and is responsive to nutritional interventions. Therefore, further investigation of this pathway in disease models and in humans may ultimately yield tailored diagnostic strategies and therapies for specific pathological states.

Original languageEnglish (US)
Pages (from-to)H1060-H1076
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume304
Issue number8
DOIs
StatePublished - Jun 10 2013

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Keywords

  • CoA transferase/SCOT
  • HMGCS2
  • Lipogenesis
  • Mitochondrial function
  • Substrate competition

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