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

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Science  16 Oct 2020:
Vol. 370, Issue 6514, pp. 364-368
DOI: 10.1126/science.abc8861

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Metabolomics, at the heart

With heart failure a leading cause of death, a better understanding of metabolic function in the heart is a welcome advance. Murashige et al. measured more than 270 metabolites using liquid chromatography–mass spectrometry in human blood samples taken from an artery entering the heart and from a vein leaving it. Differences thus reflected the metabolic processes at work in the heart. Their results confirmed that hearts voraciously consume fatty acids. Hearts secreted, rather than consumed, amino acids, thus revealing active proteolysis. In patients with heart failure, ketone and lactate consumption increased, as did proteolysis. These findings could lead to strategies for fighting heart disease by altering metabolism.

Science, this issue p. 364

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.

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