Title | Comprehensive quantification of fuel use by the failing and nonfailing human heart. |
Publication Type | Journal Article |
Year of Publication | 2020 |
Authors | Murashige, D, Jang, C, Neinast, M, Edwards, JJ, Cowan, A, Hyman, MC, Rabinowitz, JD, Frankel, DS, Arany, Z |
Journal | Science |
Volume | 370 |
Issue | 6514 |
Pagination | 364-368 |
Date Published | 2020 Oct 16 |
ISSN | 1095-9203 |
Keywords | Acetates, 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> |
DOI | 10.1126/science.abc8861 |
Alternate Journal | Science |
PubMed ID | 33060364 |
PubMed Central ID | PMC7871704 |
Grant List | R01 DK114103 / DK / NIDDK NIH HHS / United States DP1 DK113643 / DK / NIDDK NIH HHS / United States F30 HL142186 / HL / NHLBI NIH HHS / United States T32 HL007915 / HL / NHLBI NIH HHS / United States R01 HL126797 / HL / NHLBI NIH HHS / United States P30 DK019525 / DK / NIDDK NIH HHS / United States R01 HL152446 / HL / NHLBI NIH HHS / United States |