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

TitleComprehensive quantification of fuel use by the failing and nonfailing human heart.
Publication TypeJournal Article
Year of Publication2020
AuthorsMurashige, D, Jang, C, Neinast, M, Edwards, JJ, Cowan, A, Hyman, MC, Rabinowitz, JD, Frankel, DS, Arany, Z
JournalScience
Volume370
Issue6514
Pagination364-368
Date Published2020 10 16
ISSN1095-9203
KeywordsAcetates, Aged, Blood Glucose, Citric Acid Cycle, Fatty Acids, Female, Glutamic Acid, Glutamine, Heart Failure, Humans, Ketones, Leg, Male, Metabolomics, Middle Aged, Myocardial Contraction, Myocardium, Proteolysis
Abstract

<p>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.</p>

DOI10.1126/science.abc8861
Alternate JournalScience
PubMed ID33060364
Grant ListP30 DK019525 / DK / NIDDK NIH HHS / United States
F30 HL142186 / HL / NHLBI NIH HHS / United States
R01 HL126797 / HL / NHLBI NIH HHS / United States
DP1 DK113643 / DK / NIDDK NIH HHS / United States
T32 HL007915 / HL / NHLBI NIH HHS / United States
R01 DK114103 / DK / NIDDK NIH HHS / United States
R01 HL152446 / HL / NHLBI NIH HHS / United States