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Ketone Bodies and Cardiovascular Disease: An Alternate Fuel Source to the Rescue

The increased metabolic activity of the heart as a pump involves a high demand of mitochondrial adenosine triphosphate (ATP) production for its mechanical and electrical activities accomplished mainly via oxidative phosphorylation, supplying up to 95% of the necessary ATP production, with the rest a...

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Autores principales: Manolis, Antonis S., Manolis, Theodora A., Manolis, Antonis A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9962558/
https://www.ncbi.nlm.nih.gov/pubmed/36834946
http://dx.doi.org/10.3390/ijms24043534
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author Manolis, Antonis S.
Manolis, Theodora A.
Manolis, Antonis A.
author_facet Manolis, Antonis S.
Manolis, Theodora A.
Manolis, Antonis A.
author_sort Manolis, Antonis S.
collection PubMed
description The increased metabolic activity of the heart as a pump involves a high demand of mitochondrial adenosine triphosphate (ATP) production for its mechanical and electrical activities accomplished mainly via oxidative phosphorylation, supplying up to 95% of the necessary ATP production, with the rest attained by substrate-level phosphorylation in glycolysis. In the normal human heart, fatty acids provide the principal fuel (40–70%) for ATP generation, followed mainly by glucose (20–30%), and to a lesser degree (<5%) by other substrates (lactate, ketones, pyruvate and amino acids). Although ketones contribute 4–15% under normal situations, the rate of glucose use is drastically diminished in the hypertrophied and failing heart which switches to ketone bodies as an alternate fuel which are oxidized in lieu of glucose, and if adequately abundant, they reduce myocardial fat delivery and usage. Increasing cardiac ketone body oxidation appears beneficial in the context of heart failure (HF) and other pathological cardiovascular (CV) conditions. Also, an enhanced expression of genes crucial for ketone break down facilitates fat or ketone usage which averts or slows down HF, potentially by avoiding the use of glucose-derived carbon needed for anabolic processes. These issues of ketone body utilization in HF and other CV diseases are herein reviewed and pictorially illustrated.
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spelling pubmed-99625582023-02-26 Ketone Bodies and Cardiovascular Disease: An Alternate Fuel Source to the Rescue Manolis, Antonis S. Manolis, Theodora A. Manolis, Antonis A. Int J Mol Sci Review The increased metabolic activity of the heart as a pump involves a high demand of mitochondrial adenosine triphosphate (ATP) production for its mechanical and electrical activities accomplished mainly via oxidative phosphorylation, supplying up to 95% of the necessary ATP production, with the rest attained by substrate-level phosphorylation in glycolysis. In the normal human heart, fatty acids provide the principal fuel (40–70%) for ATP generation, followed mainly by glucose (20–30%), and to a lesser degree (<5%) by other substrates (lactate, ketones, pyruvate and amino acids). Although ketones contribute 4–15% under normal situations, the rate of glucose use is drastically diminished in the hypertrophied and failing heart which switches to ketone bodies as an alternate fuel which are oxidized in lieu of glucose, and if adequately abundant, they reduce myocardial fat delivery and usage. Increasing cardiac ketone body oxidation appears beneficial in the context of heart failure (HF) and other pathological cardiovascular (CV) conditions. Also, an enhanced expression of genes crucial for ketone break down facilitates fat or ketone usage which averts or slows down HF, potentially by avoiding the use of glucose-derived carbon needed for anabolic processes. These issues of ketone body utilization in HF and other CV diseases are herein reviewed and pictorially illustrated. MDPI 2023-02-10 /pmc/articles/PMC9962558/ /pubmed/36834946 http://dx.doi.org/10.3390/ijms24043534 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Manolis, Antonis S.
Manolis, Theodora A.
Manolis, Antonis A.
Ketone Bodies and Cardiovascular Disease: An Alternate Fuel Source to the Rescue
title Ketone Bodies and Cardiovascular Disease: An Alternate Fuel Source to the Rescue
title_full Ketone Bodies and Cardiovascular Disease: An Alternate Fuel Source to the Rescue
title_fullStr Ketone Bodies and Cardiovascular Disease: An Alternate Fuel Source to the Rescue
title_full_unstemmed Ketone Bodies and Cardiovascular Disease: An Alternate Fuel Source to the Rescue
title_short Ketone Bodies and Cardiovascular Disease: An Alternate Fuel Source to the Rescue
title_sort ketone bodies and cardiovascular disease: an alternate fuel source to the rescue
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9962558/
https://www.ncbi.nlm.nih.gov/pubmed/36834946
http://dx.doi.org/10.3390/ijms24043534
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