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

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

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)364-368
Number of pages5
JournalScience
Volume370
Issue number6514
DOIs
StatePublished - Oct 16 2020

All Science Journal Classification (ASJC) codes

  • General

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