Cited by 580Cardiovascular Function and Risk FactorsMetabolomics and Mass Spectrometry StudiesHeart Failure Treatment and Management

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Comprehensive quantification of fuel use by the failing and nonfailing human heart

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Murashige, Danielle, Jang, Cholsoon, Neinast, Michael, Edwards, Jonathan J., Cowan, Alexis, Hyman, Matthew C., Rabinowitz, Joshua D., Frankel, David S., Arany, Zolt·2020·Science

DOI 10.1126/science.abc8861PMC PMC7871704

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Abstract

The heart consumes circulating nutrients to fuel lifelong contraction, but a comprehensive mapping of human cardiac fuel use is lacking. We used metabolomics on blood from artery, coronary sinus, and femoral vein in 110 patients with or without heart failure to quantify the uptake and release of 277 metabolites, including all major nutrients, by the human heart and leg. The heart primarily consumed fatty acids and, unexpectedly, little glucose; secreted glutamine and other nitrogen-rich amino acids, indicating active protein breakdown, at a rate ~10 times that of the leg; and released intermediates of the tricarboxylic acid cycle, balancing anaplerosis from amino acid breakdown. Both heart and leg consumed ketones, glutamate, and acetate in direct proportionality to circulating levels, indicating that availability is a key driver for consumption of these substrates. The failing heart consumed more ketones and lactate and had higher rates of proteolysis. These data provide a comprehensive and quantitative picture of human cardiac fuel use.

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Mitochondrial Pathophysiology of Heart Failure with Reduced Ejection Fraction: From Quality Control Failure to Emerging TherapiesPreprint
Sendrowski, D., & Kozłowski, D. (2026) · doi:10.20517/scierxiv202611.0959.v1

Authors: Murashige, D., Jang, C., Neinast, M., Edwards, J. J., Cowan, A., Hyman, M. C., Rabinowitz, J. D., Frankel, D. S., & Arany, Z.
Affiliations: University of Pennsylvania (US)
Princeton University (US)
Children's Hospital of Philadelphia (US)
Perelman School of Medicine, Cardiovascular Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
ORCID: Murashige, Danielle
Jang, Cholsoon
Neinast, Michael
Edwards, Jonathan J.
Cowan, Alexis
Hyman, Matthew C.
Rabinowitz, Joshua D.
Frankel, David S.
Arany, Zolt
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 2020-10-16
Volume: 370
Issue: 6514
Pages: 364-368
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.abc8861
PMC: PMC7871704
OpenAlex: W3092932642
Cited by: 580
References: 47
Citations by year: 2026: 84 · 2025: 120 · 2024: 121 · 2023: 100 · 2022: 77 · 2021: 71 · 2020: 7
FWCI: 39.45
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Science (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
eScholarship (California Digital Library) (submittedVersion)
Funders: National Institutes of Health (1DP1DK113643)
American Diabetes Association (1-17-PDF-076)
National Heart, Lung, and Blood Institute (HL126797, 5T32HL007915, HL142186-01A1)
National Institute of Diabetes and Digestive and Kidney Diseases (DK114103)
Diabetes Research Center (P30 DK019525)
Blavatnik Family Foundation
Topics: Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
Keywords: heart failure, human heart, myocardial metabolism, fatty acid uptake, glucose uptake, amino acid catabolism, TCA cycle, anaplerosis, ketone bodies, lactate, acetate, glutamate, metabolomics
MeSH terms: Acetates, Aged, Blood Glucose, Citric Acid Cycle, Fatty Acids, Female, Glutamine, Heart Failure, Humans, Ketones, Leg, Male, Middle Aged, Myocardial Contraction, Myocardium, Glutamic Acid, Metabolomics, Proteolysis

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