Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.


Ketone bodies for the starving heart

The heart is an organ with high energy demands and metabolic flexibility, thus allowing for various energy substrates for ATP production under different physiological conditions. Zhang et al., Fernandez-Caggiano et al. and McCommis et al. converge on the mitochondrial pyruvate transporter as a key metabolic hub for the maintenance of cardiac metabolism and a critical determinant of cardiac metabolic plasticity during heart failure.

This is a preview of subscription content, access via your institution

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Fig. 1: Cardiac intermediary metabolism in normal and failing myocardium, and the role of the ketogenic diet in correcting substrate metabolism in heart failure.


  1. Krebs, H. A. Essays Biochem. 8, 1–34 (1972).

    CAS  PubMed  Google Scholar 

  2. Warburg, O. Science 123, 309–314 (1956).

    CAS  Article  Google Scholar 

  3. Vander Heiden, M. G., Cantley, L. C. & Thompson, C. B. Science 324, 1029–1033 (2009).

    Article  Google Scholar 

  4. Pavlova, N. N. & Thompson, C. B. Cell Metab. 23, 27–47 (2016).

    CAS  Article  Google Scholar 

  5. Kato, T. S. et al. Circ. Heart Fail. 4, 546–553 (2011).

    Article  Google Scholar 

  6. Depre, C. et al. Nat. Med. 4, 1269–1275 (1998).

    CAS  Article  Google Scholar 

  7. Chokshi, A. et al. Circulation 125, 2844–2853 (2012).

    CAS  Article  Google Scholar 

  8. Ji, R. et al. JCI Insight 2, e82922 (2017).

    Article  Google Scholar 

  9. Bricker, D. K. et al. Science 337, 96–100 (2012).

    CAS  Article  Google Scholar 

  10. Papa, S., Francavilla, A., Paradies, G. & Meduri, B. FEBS Lett. 12, 285–288 (1971).

    CAS  Article  Google Scholar 

  11. Eboli, M. L., Paradies, G., Galeotti, T. & Papa, S. Biochim. Biophys. Acta 460, 183–187 (1977).

    CAS  Article  Google Scholar 

  12. Schell, J. C. et al. Mol. Cell 56, 400–413 (2014).

    CAS  Article  Google Scholar 

  13. Gray, L. R. et al. Cell Metab. 22, 669–681 (2015).

    CAS  Article  Google Scholar 

  14. Zhang, Y. et al. Nat. Metab. (2020).

  15. Fernandez-Caggiano, M. et al. Nat. Metab. (2020).

  16. McCommis, K. S. et al. Nat. Metab. (2020).

  17. Abdul Kadir, A., Clarke, K. & Evans, R. D. Biochim. Biophys. Acta 1866, 165739 (2020).

    CAS  Article  Google Scholar 

  18. Cotter, D. G., Schugar, R. C. & Crawford, P. A. Am. J. Physiol. Heart Circ. Physiol. 304, H1060–H1076 (2013).

    CAS  Article  Google Scholar 

  19. Okere, I. C. et al. Hypertension 48, 1116–1123 (2006).

    CAS  Article  Google Scholar 

  20. Duda, M. K. et al. J. Card. Fail. 14, 327–335 (2008).

    CAS  Article  Google Scholar 

  21. Schugar, R. C. et al. Mol. Metab. 3, 754–769 (2014).

    CAS  Article  Google Scholar 

  22. Horton, J. L. et al. JCI Insight 4, e124079 (2019).

    Article  Google Scholar 

  23. Uchihashi, M. et al. Circ. Heart Fail. 10, e004417 (2017).

    CAS  Article  Google Scholar 

  24. Leong, H. S., Brownsey, R. W., Kulpa, J. E. & Allard, M. F. Comp. Biochem. Physiol. A Mol. Integr. Physiol. 135, 499–513 (2003).

    CAS  Article  Google Scholar 

  25. Khan, R. S. et al. Circ. Heart Fail. 5, 340–348 (2012).

    CAS  Article  Google Scholar 

  26. Bedi, K. C. Jr. et al. Circulation 133, 706–716 (2016).

    CAS  Article  Google Scholar 

  27. Ho, K. L. et al. Cardiovasc. Res. 115, 1606–1616 (2019).

    CAS  Article  Google Scholar 

  28. Ho, K.L. et al. Cardiovasc. Res. (2020).

  29. Nielsen, R. et al. Circulation 139, 2129–2141 (2019).

    CAS  Article  Google Scholar 

  30. McMurray, J. J. V. et al. N. Engl. J. Med. 381, 1995–2008 (2019).

    CAS  Article  Google Scholar 

Download references


This work was supported by a grant from the Else-Kröner Fresenius Foundation (to P.C.S.).

Author information

Authors and Affiliations


Corresponding author

Correspondence to P. Christian Schulze.

Ethics declarations

Competing interests

The authors declare no competing interests.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Schulze, P.C., Wu, J.M.F. Ketone bodies for the starving heart. Nat Metab 2, 1183–1185 (2020).

Download citation

  • Published:

  • Issue Date:

  • DOI:


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing