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Comprehensive quantification of fuel use by the failing and nonfailing human heart
Open accessAbstract
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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“The process of breaking down fatty acids to produce acetyl-CoA, known as β-oxidation, supplies the majority of acetyl-CoA for TCA cycle oxidation in certain tissues such as the heart (62).”
From Regulation and function of the mammalian tricarboxylic acid cycle (2023) · cites this paper as [62]
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Metadata
- 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
- Venue
- Science
- Published
- 2020-10-16
- Volume
- 370
- Issue
- 6514
- Pages
- 364-368
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- 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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