title: Myocardial mitochondrial and contractile function are preserved in mice lacking adiponectin.
abstract: Adiponectin deficiency leads to increased myocardial infarct size following ischemia reperfusion and to exaggerated cardiac hypertrophy following pressure overload, entities that are causally linked to mitochondrial dysfunction. In skeletal muscle, lack of adiponectin results in impaired mitochondrial function. Thus, it was our objective to investigate whether adiponectin deficiency impairs mitochondrial energetics in the heart. At 8 weeks of age, heart weight-to-body weight ratios were not different between adiponectin knockout (ADQ-/-) mice and wildtypes (WT). In isolated working hearts, cardiac output, aortic developed pressure and cardiac power were preserved in ADQ-/- mice. Rates of fatty acid oxidation, glucose oxidation and glycolysis were unchanged between groups. While myocardial oxygen consumption was slightly reduced (-24%) in ADQ-/- mice in isolated working hearts, rates of maximal ADP-stimulated mitochondrial oxygen consumption and ATP synthesis in saponin-permeabilized cardiac fibers were preserved in ADQ-/- mice with glutamate, pyruvate or palmitoyl-carnitine as a substrate. In addition, enzymatic activity of respiratory complexes I and II was unchanged between groups. Phosphorylation of AMP-activated protein kinase and SIRT1 activity were not decreased, expression and acetylation of PGC-1α were unchanged, and mitochondrial content of OXPHOS subunits was not decreased in ADQ-/- mice. Finally, increasing energy demands due to prolonged subcutaneous infusion of isoproterenol did not differentially affect cardiac contractility or mitochondrial function in ADQ-/- mice compared to WT. Thus, mitochondrial and contractile function are preserved in hearts of mice lacking adiponectin, suggesting that adiponectin may be expendable in the regulation of mitochondrial energetics and contractile function in the heart under non-pathological conditions.
authors.affiliation: Division of Cardiology and Angiology I, Heart Center Freiburg University, Freiburg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Braun
authors.affiliation: Division of Cardiology and Angiology I, Heart Center Freiburg University, Freiburg, Germany.
authors.forename: Niko
authors.initials: N
authors.lastname: Hettinger
authors.affiliation: Division of Cardiology and Angiology I, Heart Center Freiburg University, Freiburg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Koentges
authors.affiliation: Division of Cardiology and Angiology I, Heart Center Freiburg University, Freiburg, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Pfeil
authors.affiliation: Division of Cardiology and Angiology I, Heart Center Freiburg University, Freiburg, Germany.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Cimolai
authors.affiliation: Division of Cardiology and Angiology I, Heart Center Freiburg University, Freiburg, Germany; Institute for Clinical Chemistry and Laboratory Medicine, Freiburg University Hospital, Freiburg, Germany.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Hoffmann
authors.affiliation: Department of Cardiothoracic Surgery, Jena University Hospital, Jena, Germany.
authors.forename: Moritz
authors.initials: M
authors.lastname: Osterholt
authors.affiliation: Department of Cardiothoracic Surgery, Jena University Hospital, Jena, Germany.
authors.forename: Torsten
authors.initials: T
authors.lastname: Doenst
authors.affiliation: Division of Cardiology and Angiology I, Heart Center Freiburg University, Freiburg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Bode
authors.affiliation: Division of Cardiology and Angiology I, Heart Center Freiburg University, Freiburg, Germany.
authors.forename: Heiko
authors.initials: H
authors.lastname: Bugger
mesh_terms: D052242:Adiponectin / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D000818:Animals; D004734:Energy Metabolism; D006321:Heart / Q000502:physiology; D008297:Male; D008661:Metabolism, Inborn Errors / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008929:Mitochondria, Heart / Q000378:metabolism*; D009200:Myocardial Contraction / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism*
chemical_list: D052242:Adiponectin; C499919:Adipoq protein, mouse