Comprehensive quantification of fuel use by the failing and nonfailing human heart
Danielle Murashige,Cholsoon Jang,Michael D. Neinast,Jonathan J. Edwards,Alexis J. Cowan,Matthew C. Hyman,Joshua D. Rabinowitz,David S. Frankel,Zolt Arany +8 more
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TLDR
A comprehensive and quantitative picture of human cardiac fuel use is provided, using 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.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.read more
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Short chain fatty acids outpace ketone oxidation in the failing heart
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Myocardial ketone body utilization in patients with heart failure: The impact of oral ketone ester.
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TL;DR: In the brain and kidney, stable-isotope-labeled nutrient infusion to matrix-assisted laser desorption ionization imaging mass spectrometry (iso-imaging) to quantitate metabolic activity in mammalian tissues in a spatially resolved manner can reveal the spatial organization of metabolic activity.
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Branched-chain α-ketoacids are preferentially reaminated and activate protein synthesis in the heart.
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Macropinocytosis of protein is an amino acid supply route in Ras-transformed cells
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