TY - JOUR
T1 - Comprehensive quantification of fuel use by the failing and nonfailing human heart
AU - Murashige, Danielle
AU - Jang, Cholsoon
AU - Neinast, Michael
AU - Edwards, Jonathan J.
AU - Cowan, Alexis
AU - Hyman, Matthew C.
AU - Rabinowitz, Joshua D.
AU - Frankel, David S.
AU - Arany, Zolt
N1 - Funding Information:
We thank the staff of the University of Pennsylvania Electrophysiology Section for their enthusiastic support of this study, in particular M. Gnap, K. Conn, L. Tomczuk, and L. Czerniawski, as well as members of the Arany and Rabinowitz laboratories for insightful comments, in particular N. Yücel and S. Yang. Funding: D.M. was supported by the NHLBI (F30 HL142186-01A1) and the Blavatnik Family Foundation, C.J. was supported by the American Diabetes Association (1-17-PDF-076), J.J.E. was supported by NIH 5T32HL007915, J.D.R. was supported by an NIH Pioneer grant (1DP1DK113643) and an NIH Diabetes Research Center grant (P30 DK019525), and Z.A. was supported by the NHLBI (HL126797) and the NIDDK (DK114103).
Publisher Copyright:
© 2020 American Association for the Advancement of Science. All rights reserved.
PY - 2020/10/16
Y1 - 2020/10/16
N2 - 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.
AB - 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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U2 - 10.1126/science.abc8861
DO - 10.1126/science.abc8861
M3 - Article
C2 - 33060364
AN - SCOPUS:85093480567
SN - 0036-8075
VL - 370
SP - 364
EP - 368
JO - Science
JF - Science
IS - 6514
ER -