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  • Metabolic Messengers
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Metabolic Messengers: ketone bodies

Nature Metabolism volume 5, pages 2062–2074 (2023)Cite this article

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Abstract

Prospective molecular targets and therapeutic applications for ketone body metabolism have increased exponentially in the past decade. Initially considered to be restricted in scope as liver-derived alternative fuel sources during periods of carbohydrate restriction or as toxic mediators during diabetic ketotic states, ketogenesis and ketone bodies modulate cellular homeostasis in multiple physiological states through a diversity of mechanisms. Selective signalling functions also complement the metabolic fates of the ketone bodies acetoacetate and d-β-hydroxybutyrate. Here we discuss recent discoveries revealing the pleiotropic roles of ketone bodies, their endogenous sourcing, signalling mechanisms and impact on target organs, and considerations for when they are either stimulated for endogenous production by diets or pharmacological agents or administered as exogenous wellness-promoting agents.

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Fig. 1: Timeline of major discoveries related to ketone bodies.
Fig. 2: Metabolic and signalling mechanisms of ketone bodies.
Fig. 3: The effects of ketone bodies in mice versus humans.
Fig. 4: Mice and humans exhibit differing responses to fasting- and diet-induced ketosis.

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Acknowledgements

The authors are grateful for support from the National Institutes of Health (grants DK091538, AG069781, DK007203 and HL166142).

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  1. These authors contributed equally: Alisa B. Nelson, Eric D. Queathem.

Authors and Affiliations

  1. Division of Molecular Medicine, Department of Medicine, University of Minnesota, Minneapolis, MN, USA

    Alisa B. Nelson, Eric D. Queathem, Patrycja Puchalska & Peter A. Crawford

  2. Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USA

    Eric D. Queathem & Peter A. Crawford

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A.B.N., E.D.Q., P.P. and P.A.C. generated the manuscript’s outline and drafted and revised the manuscript. E.D.Q. and P.P. generated the figures.

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Nelson, A.B., Queathem, E.D., Puchalska, P. et al. Metabolic Messengers: ketone bodies. Nat Metab 5, 2062–2074 (2023). https://doi.org/10.1038/s42255-023-00935-3

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