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Fasting increases susceptibility to acute myocardial ischaemia/reperfusion injury through a sirtuin-3 mediated increase in fatty acid oxidation

Fasting increases susceptibility to acute myocardial ischaemia/reperfusion injury (IRI) but the mechanisms are unknown. Here, we investigate the role of the mitochondrial NAD(+)-dependent deacetylase, Sirtuin-3 (SIRT3), which has been shown to influence fatty acid oxidation and cardiac outcomes, as...

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Autores principales: Hall, Andrew R., Karwi, Qutuba G., Kumar, Sanjeev, Dongworth, Rachel, Aksentijević, Dunja, Altamimi, Tariq R., Fridianto, Kevin Timothy, Chinda, Kroekkiat, Hernandez-Resendiz, Sauri, Mahmood, Mohammad U., Michelakis, Evangelos, Ramachandra, Chrishan J., Ching, Jianhong, Vicencio, Jose M., Shattock, Michael J., Kovalik, Jean-Paul, Yellon, Derek M., Lopaschuk, Gary, Hausenloy, Derek J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9708654/
https://www.ncbi.nlm.nih.gov/pubmed/36446868
http://dx.doi.org/10.1038/s41598-022-23847-w
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author Hall, Andrew R.
Karwi, Qutuba G.
Kumar, Sanjeev
Dongworth, Rachel
Aksentijević, Dunja
Altamimi, Tariq R.
Fridianto, Kevin Timothy
Chinda, Kroekkiat
Hernandez-Resendiz, Sauri
Mahmood, Mohammad U.
Michelakis, Evangelos
Ramachandra, Chrishan J.
Ching, Jianhong
Vicencio, Jose M.
Shattock, Michael J.
Kovalik, Jean-Paul
Yellon, Derek M.
Lopaschuk, Gary
Hausenloy, Derek J.
author_facet Hall, Andrew R.
Karwi, Qutuba G.
Kumar, Sanjeev
Dongworth, Rachel
Aksentijević, Dunja
Altamimi, Tariq R.
Fridianto, Kevin Timothy
Chinda, Kroekkiat
Hernandez-Resendiz, Sauri
Mahmood, Mohammad U.
Michelakis, Evangelos
Ramachandra, Chrishan J.
Ching, Jianhong
Vicencio, Jose M.
Shattock, Michael J.
Kovalik, Jean-Paul
Yellon, Derek M.
Lopaschuk, Gary
Hausenloy, Derek J.
author_sort Hall, Andrew R.
collection PubMed
description Fasting increases susceptibility to acute myocardial ischaemia/reperfusion injury (IRI) but the mechanisms are unknown. Here, we investigate the role of the mitochondrial NAD(+)-dependent deacetylase, Sirtuin-3 (SIRT3), which has been shown to influence fatty acid oxidation and cardiac outcomes, as a potential mediator of this effect. Fasting was shown to shift metabolism from glucose towards fatty acid oxidation. This change in metabolic fuel substrate utilisation increased myocardial infarct size in wild-type (WT), but not SIRT3 heterozygous knock-out (KO) mice. Further analysis revealed SIRT3 KO mice were better adapted to starvation through an improved cardiac efficiency, thus protecting them from acute myocardial IRI. Mitochondria from SIRT3 KO mice were hyperacetylated compared to WT mice which may regulate key metabolic processes controlling glucose and fatty acid utilisation in the heart. Fasting and the associated metabolic switch to fatty acid respiration worsens outcomes in WT hearts, whilst hearts from SIRT3 KO mice are better adapted to oxidising fatty acids, thereby protecting them from acute myocardial IRI.
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spelling pubmed-97086542022-12-01 Fasting increases susceptibility to acute myocardial ischaemia/reperfusion injury through a sirtuin-3 mediated increase in fatty acid oxidation Hall, Andrew R. Karwi, Qutuba G. Kumar, Sanjeev Dongworth, Rachel Aksentijević, Dunja Altamimi, Tariq R. Fridianto, Kevin Timothy Chinda, Kroekkiat Hernandez-Resendiz, Sauri Mahmood, Mohammad U. Michelakis, Evangelos Ramachandra, Chrishan J. Ching, Jianhong Vicencio, Jose M. Shattock, Michael J. Kovalik, Jean-Paul Yellon, Derek M. Lopaschuk, Gary Hausenloy, Derek J. Sci Rep Article Fasting increases susceptibility to acute myocardial ischaemia/reperfusion injury (IRI) but the mechanisms are unknown. Here, we investigate the role of the mitochondrial NAD(+)-dependent deacetylase, Sirtuin-3 (SIRT3), which has been shown to influence fatty acid oxidation and cardiac outcomes, as a potential mediator of this effect. Fasting was shown to shift metabolism from glucose towards fatty acid oxidation. This change in metabolic fuel substrate utilisation increased myocardial infarct size in wild-type (WT), but not SIRT3 heterozygous knock-out (KO) mice. Further analysis revealed SIRT3 KO mice were better adapted to starvation through an improved cardiac efficiency, thus protecting them from acute myocardial IRI. Mitochondria from SIRT3 KO mice were hyperacetylated compared to WT mice which may regulate key metabolic processes controlling glucose and fatty acid utilisation in the heart. Fasting and the associated metabolic switch to fatty acid respiration worsens outcomes in WT hearts, whilst hearts from SIRT3 KO mice are better adapted to oxidising fatty acids, thereby protecting them from acute myocardial IRI. Nature Publishing Group UK 2022-11-29 /pmc/articles/PMC9708654/ /pubmed/36446868 http://dx.doi.org/10.1038/s41598-022-23847-w Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Hall, Andrew R.
Karwi, Qutuba G.
Kumar, Sanjeev
Dongworth, Rachel
Aksentijević, Dunja
Altamimi, Tariq R.
Fridianto, Kevin Timothy
Chinda, Kroekkiat
Hernandez-Resendiz, Sauri
Mahmood, Mohammad U.
Michelakis, Evangelos
Ramachandra, Chrishan J.
Ching, Jianhong
Vicencio, Jose M.
Shattock, Michael J.
Kovalik, Jean-Paul
Yellon, Derek M.
Lopaschuk, Gary
Hausenloy, Derek J.
Fasting increases susceptibility to acute myocardial ischaemia/reperfusion injury through a sirtuin-3 mediated increase in fatty acid oxidation
title Fasting increases susceptibility to acute myocardial ischaemia/reperfusion injury through a sirtuin-3 mediated increase in fatty acid oxidation
title_full Fasting increases susceptibility to acute myocardial ischaemia/reperfusion injury through a sirtuin-3 mediated increase in fatty acid oxidation
title_fullStr Fasting increases susceptibility to acute myocardial ischaemia/reperfusion injury through a sirtuin-3 mediated increase in fatty acid oxidation
title_full_unstemmed Fasting increases susceptibility to acute myocardial ischaemia/reperfusion injury through a sirtuin-3 mediated increase in fatty acid oxidation
title_short Fasting increases susceptibility to acute myocardial ischaemia/reperfusion injury through a sirtuin-3 mediated increase in fatty acid oxidation
title_sort fasting increases susceptibility to acute myocardial ischaemia/reperfusion injury through a sirtuin-3 mediated increase in fatty acid oxidation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9708654/
https://www.ncbi.nlm.nih.gov/pubmed/36446868
http://dx.doi.org/10.1038/s41598-022-23847-w
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