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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Insulin signaling in the heart.
TL;DR: In this article, the authors present the multiple roles of insulin signaling in cardiac physiology and pathology and discuss the potential therapeutic consequences of modulating myocardial insulin signaling, including increased risk of heart failure in obesity and diabetes.
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Prolonged Exposure to Microgravity Reduces Cardiac Contractility and Initiates Remodeling in Drosophila
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TL;DR: Effect of dapagliflozin on key metabolic pathways, supporting a role for altered ketone and fatty acid biology with sodium-glucose cotransporter-2 inhibitors in patients with HFrEF, is observed.
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Integrated landscape of cardiac metabolism in end-stage human nonischemic dilated cardiomyopathy
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