Journal article
Myocardial mitochondrial dysfunction in mice lacking adiponectin receptor 1
Basic research in cardiology, Vol.110(4), pp.1-17
07/2015
DOI: 10.1007/s00395-015-0495-4
PMID: 25982881
Abstract
Hypoadiponectinemia is an independent predictor of cardiovascular disease, impairs mitochondrial function in skeletal muscle, and has been linked to the pathogenesis of Type 2 diabetes. In models of Type 2 diabetes, myocardial mitochondrial function is impaired, which is improved by increasing serum adiponectin levels. We aimed to define the roles of adiponectin receptor 1 (AdipoR1) and 2 (AdipoR2) in adiponectin-evoked regulation of mitochondrial function in the heart. In isolated working hearts in mice lacking AdipoR1, myocardial oxygen consumption was increased without a concomitant increase in cardiac work, resulting in reduced cardiac efficiency. Activities of mitochondrial oxidative phosphorylation (OXPHOS) complexes were reduced, accompanied by reduced OXPHOS protein levels, phosphorylation of AMP-activated protein kinase, sirtuin 1 activity, and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) signaling. Decreased ATP/O ratios suggested myocardial mitochondrial uncoupling in AdipoR1-deficient mice, which was normalized by lowering increased mitochondrial 4-hydroxynonenal levels following treatment with the mitochondria-targeted antioxidant Mn (III) tetrakis (4-benzoic acid) porphyrin. Lack of AdipoR2 did not impair mitochondrial function and coupling in the heart. Thus, lack of AdipoR1 impairs myocardial mitochondrial function and coupling, suggesting that impaired AdipoR1 signaling may contribute to mitochondrial dysfunction and mitochondrial uncoupling in Type 2 diabetic hearts.
Details
- Title: Subtitle
- Myocardial mitochondrial dysfunction in mice lacking adiponectin receptor 1
- Creators
- Christoph Koentges - Division of Cardiology and Angiology I Heart Center Freiburg University Hugstetter Str. 55 79106 Freiburg GermanyAlexandra König - Division of Cardiology and Angiology I Heart Center Freiburg University Hugstetter Str. 55 79106 Freiburg GermanyKatharina Pfeil - Division of Cardiology and Angiology I Heart Center Freiburg University Hugstetter Str. 55 79106 Freiburg GermanyMaximilian Hölscher - Division of Cardiology and Angiology I Heart Center Freiburg University Hugstetter Str. 55 79106 Freiburg GermanyTilman Schnick - Institute of Experimental and Clinical Pharmacology University of Freiburg Freiburg GermanyAdam Wende - Department of Molecular and Cellular Pathology University of Alabama at Birmingham Birmingham AL USAAndrea Schrepper - Department of Cardiothoracic Surgery Jena University Hospital Jena GermanyMaria Cimolai - Division of Cardiology and Angiology I Heart Center Freiburg University Hugstetter Str. 55 79106 Freiburg GermanySophia Kersting - Division of Cardiology and Angiology I Heart Center Freiburg University Hugstetter Str. 55 79106 Freiburg GermanyMichael Hoffmann - Institute for Clinical Chemistry and Laboratory Medicine Freiburg University Hospital Freiburg GermanyJudith Asal - Division of Cardiology and Angiology I Heart Center Freiburg University Hugstetter Str. 55 79106 Freiburg GermanyMoritz Osterholt - Department of Cardiothoracic Surgery Jena University Hospital Jena GermanyKatja Odening - Division of Cardiology and Angiology I Heart Center Freiburg University Hugstetter Str. 55 79106 Freiburg GermanyTorsten Doenst - Department of Cardiothoracic Surgery Jena University Hospital Jena GermanyLutz Hein - Institute of Experimental and Clinical Pharmacology University of Freiburg Freiburg GermanyE Abel - Fraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism Carver College of Medicine, University of Iowa Iowa City IA USAChristoph Bode - Division of Cardiology and Angiology I Heart Center Freiburg University Hugstetter Str. 55 79106 Freiburg GermanyHeiko Bugger - Division of Cardiology and Angiology I Heart Center Freiburg University Hugstetter Str. 55 79106 Freiburg Germany
- Resource Type
- Journal article
- Publication Details
- Basic research in cardiology, Vol.110(4), pp.1-17
- Publisher
- Springer Berlin Heidelberg; Berlin/Heidelberg
- DOI
- 10.1007/s00395-015-0495-4
- PMID
- 25982881
- ISSN
- 0300-8428
- eISSN
- 1435-1803
- Language
- English
- Date published
- 07/2015
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984025274002771
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