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GCN5L1 impairs diastolic function in mice exposed to a high fat diet by restricting cardiac pyruvate oxidation

dc.contributor.authorDharendra Thapa
dc.contributor.authorParamesha Bugga
dc.contributor.authorBellina A. S. Mushala
dc.contributor.authorJanet R. Manning
dc.contributor.authorMichael W. Stoner
dc.contributor.authorBrenda McMahon
dc.contributor.authorXuemei Zeng
dc.contributor.authorPamela S. Cantrell
dc.contributor.authorNathan Yates
dc.contributor.authorBingxian Xie
dc.contributor.authorLia R. Edmunds
dc.contributor.authorMichael J. Jurczak
dc.contributor.authorIain Scott
dc.contributor.otherDivision of Exercise Physiology West Virginia University School of Medicine Morgantown West Virginia USA
dc.contributor.otherVascular Medicine Institute Pittsburgh Pennsylvania USA
dc.contributor.otherVascular Medicine Institute Pittsburgh Pennsylvania USA
dc.contributor.otherVascular Medicine Institute Pittsburgh Pennsylvania USA
dc.contributor.otherVascular Medicine Institute Pittsburgh Pennsylvania USA
dc.contributor.otherVascular Medicine Institute Pittsburgh Pennsylvania USA
dc.contributor.otherBiomedical Mass Spectrometry Center, Schools of the Health Sciences University of Pittsburgh Pittsburgh Pennsylvania USA
dc.contributor.otherBiomedical Mass Spectrometry Center, Schools of the Health Sciences University of Pittsburgh Pittsburgh Pennsylvania USA
dc.contributor.otherBiomedical Mass Spectrometry Center, Schools of the Health Sciences University of Pittsburgh Pittsburgh Pennsylvania USA
dc.contributor.otherCenter for Metabolism and Mitochondrial Medicine, Department of Medicine University of Pittsburgh Pittsburgh Pennsylvania USA
dc.contributor.otherCenter for Metabolism and Mitochondrial Medicine, Department of Medicine University of Pittsburgh Pittsburgh Pennsylvania USA
dc.contributor.otherCenter for Metabolism and Mitochondrial Medicine, Department of Medicine University of Pittsburgh Pittsburgh Pennsylvania USA
dc.contributor.otherVascular Medicine Institute Pittsburgh Pennsylvania USA
dc.date.accessioned2022-08-11T07:18:31Z
dc.date.accessioned2025-10-08T08:27:18Z
dc.date.available2025-10-08T08:27:18Z
dc.date.issued01-08-2022
dc.identifier.urihttp://digilib.fisipol.ugm.ac.id/repo/handle/15717717/35940
dc.description.abstractAbstract Left ventricular diastolic dysfunction is a structural and functional condition that precedes the development of heart failure with preserved ejection fraction (HFpEF). The etiology of diastolic dysfunction includes alterations in fuel substrate metabolism that negatively impact cardiac bioenergetics, and may precipitate the eventual transition to heart failure. To date, the molecular mechanisms that regulate early changes in fuel metabolism leading to diastolic dysfunction remain unclear. In this report, we use a diet‐induced obesity model in aged mice to show that inhibitory lysine acetylation of the pyruvate dehydrogenase (PDH) complex promotes energetic deficits that may contribute to the development of diastolic dysfunction in mouse hearts. Cardiomyocyte‐specific deletion of the mitochondrial lysine acetylation regulatory protein GCN5L1 prevented hyperacetylation of the PDH complex subunit PDHA1, allowing aged obese mice to continue using pyruvate as a bioenergetic substrate in the heart. Our findings suggest that changes in mitochondrial protein lysine acetylation represent a key metabolic component of diastolic dysfunction that precedes the development of heart failure.
dc.language.isoEN
dc.publisherWiley
dc.subject.lccPhysiology
dc.titleGCN5L1 impairs diastolic function in mice exposed to a high fat diet by restricting cardiac pyruvate oxidation
dc.typeArticle
dc.description.keywordsacetylation
dc.description.keywordsdiastolic dysfunction
dc.description.keywordsheart failure
dc.description.keywordsmitochondria
dc.description.keywordspyruvate dehydrogenase
dc.description.pagesn/a-n/a
dc.description.doi10.14814/phy2.15415
dc.title.journalPhysiological Reports
dc.identifier.e-issn2051-817X
dc.identifier.oai6a55ab8d84e5441b8d4eb92811819642
dc.journal.infoVolume 10, Issue 15


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