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

Autor: Hall AR; The Hatter Cardiovascular Institute, University College London, London, UK., Karwi QG; Cardiovascular Research Centre, University of Alberta, 423 Heritage Medical Research Centre, Edmonton, AB, T6G 2S2, Canada., Kumar S; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA., Dongworth R; The Hatter Cardiovascular Institute, University College London, London, UK., Aksentijević D; William Harvey Research Institute, Centre for Biochemical Pharmacology, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London, UK., Altamimi TR; Cardiovascular Research Centre, University of Alberta, 423 Heritage Medical Research Centre, Edmonton, AB, T6G 2S2, Canada., Fridianto KT; Cardiovascular & Metabolic Disorders Program, Duke-National University of Singapore Medical School, 8 College Road, Singapore, 169857, Singapore., Chinda K; Department of Physiology, Faculty of Medical Science, Naresuan University, Phitsanulok, Thailand., Hernandez-Resendiz S; National Heart Research Institute Singapore, National Heart Centre, Singapore, Singapore.; Department of Medicine, University of Alberta, Edmonton, AB, T6G 2B7, Canada., Mahmood MU; Cardiovascular Research Centre, University of Alberta, 423 Heritage Medical Research Centre, Edmonton, AB, T6G 2S2, Canada., Michelakis E; School of Cardiovascular Medicine and Sciences, British Heart Foundation Centre of Research Excellence, King's College London, The Rayne Institute, St Thomas' Hospital, London, UK., Ramachandra CJ; Cardiovascular & Metabolic Disorders Program, Duke-National University of Singapore Medical School, 8 College Road, Singapore, 169857, Singapore.; National Heart Research Institute Singapore, National Heart Centre, Singapore, Singapore., Ching J; Cardiovascular & Metabolic Disorders Program, Duke-National University of Singapore Medical School, 8 College Road, Singapore, 169857, Singapore., Vicencio JM; The Hatter Cardiovascular Institute, University College London, London, UK., Shattock MJ; School of Cardiovascular Medicine and Sciences, British Heart Foundation Centre of Research Excellence, King's College London, The Rayne Institute, St Thomas' Hospital, London, UK., Kovalik JP; Cardiovascular & Metabolic Disorders Program, Duke-National University of Singapore Medical School, 8 College Road, Singapore, 169857, Singapore., Yellon DM; The Hatter Cardiovascular Institute, University College London, London, UK., Lopaschuk G; Cardiovascular Research Centre, University of Alberta, 423 Heritage Medical Research Centre, Edmonton, AB, T6G 2S2, Canada., Hausenloy DJ; The Hatter Cardiovascular Institute, University College London, London, UK. derek.hausenloy@duke-nus.edu.sg.; Cardiovascular & Metabolic Disorders Program, Duke-National University of Singapore Medical School, 8 College Road, Singapore, 169857, Singapore. derek.hausenloy@duke-nus.edu.sg.; National Heart Research Institute Singapore, National Heart Centre, Singapore, Singapore. derek.hausenloy@duke-nus.edu.sg.; Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore. derek.hausenloy@duke-nus.edu.sg.; Chengdu University, Chengdu, China. derek.hausenloy@duke-nus.edu.sg.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2022 Nov 29; Vol. 12 (1), pp. 20551. Date of Electronic Publication: 2022 Nov 29.
DOI: 10.1038/s41598-022-23847-w
Abstrakt: 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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