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Myocardial mitochondrial and contractile function are preserved in mice lacking adiponectin.

Braun M, Hettinger N, Koentges C, Pfeil K, Cimolai MC, Hoffmann MM, Osterholt M, Doenst T, Bode C, Bugger H - PLoS ONE (2015)

Bottom Line: In skeletal muscle, lack of adiponectin results in impaired mitochondrial function.Rates of fatty acid oxidation, glucose oxidation and glycolysis were unchanged between groups.In addition, enzymatic activity of respiratory complexes I and II was unchanged between groups.

View Article: PubMed Central - PubMed

Affiliation: Division of Cardiology and Angiology I, Heart Center Freiburg University, Freiburg, Germany.

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.

No MeSH data available.


Related in: MedlinePlus

Preserved mitochondrial morphology in ADQ-/- hearts.Representative electron microscopy images at magnification x 2000 or x 40000 (A), and stereologic quantification of mitochondrial volume density (B) of 8 week-old ADQ-/- and WT hearts; n = 4. * p<0.05 vs. WT.
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pone.0119416.g004: Preserved mitochondrial morphology in ADQ-/- hearts.Representative electron microscopy images at magnification x 2000 or x 40000 (A), and stereologic quantification of mitochondrial volume density (B) of 8 week-old ADQ-/- and WT hearts; n = 4. * p<0.05 vs. WT.

Mentions: Mitochondrial function was evaluated in saponin-permeabilized cardiac fibers. V0, VADP and VOligo were unchanged between ADQ-/- and WT mice, using palmitoyl-carnitine, glutamate or pyruvate as substrate (Fig. 2). Similarly, rates of ATP synthesis were unchanged between groups with any substrate, resulting in unchanged ATP/O ratios (Fig. 2). In addition, we determined enzymatic activities of OXPHOS complexes. While complex IV showed a significant decrease in enzymatic activity, activities of complexes I and II were unchanged (Fig. 3). Mitochondrial ultrastructure was analyzed using electron microscopy. Mitochondria were embedded in regular fashion between myofibers without disarrays, and cristae density and membrane morphology appeared identical in ADQ-/- and WT mice (Fig. 4). Mitochondrial volume density was even slightly increased in ADQ-/- mice (Fig. 4). Taken together, mitochondrial function was preserved in hearts of ADQ-/- mice.


Myocardial mitochondrial and contractile function are preserved in mice lacking adiponectin.

Braun M, Hettinger N, Koentges C, Pfeil K, Cimolai MC, Hoffmann MM, Osterholt M, Doenst T, Bode C, Bugger H - PLoS ONE (2015)

Preserved mitochondrial morphology in ADQ-/- hearts.Representative electron microscopy images at magnification x 2000 or x 40000 (A), and stereologic quantification of mitochondrial volume density (B) of 8 week-old ADQ-/- and WT hearts; n = 4. * p<0.05 vs. WT.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4364743&req=5

pone.0119416.g004: Preserved mitochondrial morphology in ADQ-/- hearts.Representative electron microscopy images at magnification x 2000 or x 40000 (A), and stereologic quantification of mitochondrial volume density (B) of 8 week-old ADQ-/- and WT hearts; n = 4. * p<0.05 vs. WT.
Mentions: Mitochondrial function was evaluated in saponin-permeabilized cardiac fibers. V0, VADP and VOligo were unchanged between ADQ-/- and WT mice, using palmitoyl-carnitine, glutamate or pyruvate as substrate (Fig. 2). Similarly, rates of ATP synthesis were unchanged between groups with any substrate, resulting in unchanged ATP/O ratios (Fig. 2). In addition, we determined enzymatic activities of OXPHOS complexes. While complex IV showed a significant decrease in enzymatic activity, activities of complexes I and II were unchanged (Fig. 3). Mitochondrial ultrastructure was analyzed using electron microscopy. Mitochondria were embedded in regular fashion between myofibers without disarrays, and cristae density and membrane morphology appeared identical in ADQ-/- and WT mice (Fig. 4). Mitochondrial volume density was even slightly increased in ADQ-/- mice (Fig. 4). Taken together, mitochondrial function was preserved in hearts of ADQ-/- mice.

Bottom Line: In skeletal muscle, lack of adiponectin results in impaired mitochondrial function.Rates of fatty acid oxidation, glucose oxidation and glycolysis were unchanged between groups.In addition, enzymatic activity of respiratory complexes I and II was unchanged between groups.

View Article: PubMed Central - PubMed

Affiliation: Division of Cardiology and Angiology I, Heart Center Freiburg University, Freiburg, Germany.

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.

No MeSH data available.


Related in: MedlinePlus