Myocardial Mitochondrial and Contractile Function Are Preserved in Mice Lacking Adiponectin

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.脂联素（adiponectin）缺乏会导致缺血再灌注后心肌梗死面积增大，以及压力超负荷后心脏肥大加剧，而这些病症均与线粒体功能障碍存在因果关联。在骨骼肌中，脂联素缺乏会引发线粒体功能受损。因此本研究旨在探究脂联素缺乏是否会损害心脏的线粒体能量代谢。 8周龄时，脂联素敲除（adiponectin knockout, ADQ-/-）小鼠与野生型（wildtype, WT）小鼠的心脏重量/体重比值无显著差异。在离体工作心脏模型中，ADQ-/-小鼠的心输出量、主动脉峰值压力与心脏功率均保持正常。两组小鼠的脂肪酸氧化、葡萄糖氧化及糖酵解速率均无显著变化。尽管在离体工作心脏模型中，ADQ-/-小鼠的心肌耗氧量略有降低（降幅达24%），但当以谷氨酸、丙酮酸或棕榈酰肉碱作为底物时，皂素透化心肌纤维中ADP最大刺激的线粒体耗氧速率与ATP合成速率均保持正常。 此外，两组小鼠的呼吸链复合物I与复合物II的酶活性均无显著变化。ADQ-/-小鼠的AMP活化蛋白激酶（AMP-activated protein kinase）磷酸化水平与SIRT1活性均未降低，PGC-1α的表达与乙酰化水平无显著变化，且线粒体氧化磷酸化（OXPHOS）亚基的含量也未减少。 最后，相较于野生型小鼠，长期皮下输注异丙肾上腺素所引发的能量需求增加，并未对ADQ-/-小鼠的心脏收缩功能或线粒体功能造成差异性影响。 综上，脂联素缺乏小鼠的心脏线粒体与收缩功能均保持正常，这表明在非病理状态下，脂联素对于心脏线粒体能量代谢与收缩功能的调控或许并非必需。