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METABOLISM

Quantification of fuel use in the human heart

Nature Reviews Cardiology volume 18, page 3 (2021)Cite this article

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The healthy heart consumes less glucose than previously reported, while uptake of ketones in the failing heart is substantial, according to a study published in Science. Zolt Arany and colleagues comprehensively quantified the uptake and release of 277 metabolites from 110 individuals with or without heart failure. “We have long been interested in cardiac metabolism, and in particular understanding why the failing heart appears to be an ‘engine out of fuel’ despite having access to plenty of fuel. The first step in answering that is obviously to understand in depth what a human heart consumes as fuel. The advent of modern, highly precise mass spectrometry made that possible in a way never done before.”

The heart consumed all free fatty acid (FFA) types, whereas the leg primarily took up saturated FFAs and released unsaturated FFAs. Although the leg took up glucose, there was no average net glucose uptake by the heart. “This finding contradicts all previous studies that have examined glucose use by the heart,” comments Gary Lopaschuk (University of Alberta, Canada), who was not involved in this study. Arany and colleagues found that ~85% of cardiac ATP production comes from fatty acids (~57% from FFAs and ~28% from lipoprotein-derived fatty acids), 6.4% from ketones, 4.6% from amino acids and 2.8% from lactate. Interestingly, cardiac proteolysis was tenfold higher in the heart than in the leg, and the heart strongly excreted amino acids with high nitrogen content. “We found, as expected, that the heart largely consumes fats. What surprised us, however, was the extent to which the heart also seems to break down protein as a source of fuel. Part of the reason may be that the patients were fasting (as is obligatory for clinical procedures), but nevertheless the heart could have chosen to use sources other than protein,” remarks Arany.

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References

Original article

  • Murashige, D. et al. Comprehensive quantification of fuel use by the failing and nonfailing human heart. Science 370, 364–368 (2020)

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Related article

  • Bertero, E. & Maack, C. Metabolic remodelling in heart failure. Nat. Rev. Cardiol. 15, 457–470 (2018)

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  1. Nature Reviews Cardiology http://www.nature.com/nrcardio/

    Andrew Robson

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  1. Andrew Robson
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Correspondence to Andrew Robson.

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Robson, A. Quantification of fuel use in the human heart. Nat Rev Cardiol 18, 3 (2021). https://doi.org/10.1038/s41569-020-00476-2

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