Adiponectin is one of the most abundant circulating hormones, which through adenosine monophosphate-activated protein kinase (AMPK), enhances fatty acid and glucose oxidation, and exerts a cardioprotective effect. However, its effects on cellular bioenergetics have not been explored. We have previously reported that 5-aminoimidazole-4-carboxamide 1-β-D-ribofuranoside (AICAR, an AMPK activator) enhances mitochondrial respiration through a succinate dehydrogenase (SDH or complex II)-dependent mechanism in cardiac myocytes, leading us to predict that Adiponectin would exert a similar effect via activating AMPK. Our results show that Adiponectin enhances basal mitochondrial oxygen consumption rate (OCR), ATP production, and spare respiratory capacity (SRC), which were all abolished by the knockdown of AMPKγ1, inhibition of SDH complex assembly, via the knockdown of the SDH assembly factor 1 (Sdhaf1), or inhibition of SDH activity. Additionally, Adiponectin alleviated hypoxia-induced reductions in OCR and ATP production, in a Sdhaf1-dependent manner, whereas overexpression of Sdhaf1 confirmed its sufficiency for mediating these effects. Importantly, the levels of holoenzyme SDH under the various conditions correlated with OCR. We also show that the effects of Adiponectin, AMPK, Sdhaf1, as well as, SDH complex assembly all required sirtuin 3 (Sirt3). In conclusion, Adiponectin potentiates mitochondrial bioenergetics via promoting SDH complex assembly in an AMPK-, Sdhaf1-, and Sirt3-dependent fashion in cardiac myocytes.

脂联素是最丰富的循环激素之一，它通过磷酸腺苷激活蛋白激酶 (AMPK)，增强脂肪酸和葡萄糖的氧化，发挥心脏保护作用。然而，其对细胞生物能量学的影响尚未得到探索。我们之前曾报道，5-氨基咪唑-4-甲酰胺 1-β-D-呋喃核糖苷（AICAR，一种 AMPK 激活剂）通过心肌细胞中琥珀酸脱氢酶（SDH 或复合物 II）依赖性机制增强线粒体呼吸，使我们预测脂联素会通过激活 AMPK 发挥类似的作用。我们的结果表明，脂联素提高了基础线粒体耗氧率 (OCR)、ATP 产生和备用呼吸能力 (SRC)，这些都被 AMPKγ1 的敲低、SDH 复合物组装的抑制、通过 SDH 组装因子 1 (Sdhaf1) 的敲低或 SDH 活性的抑制。此外，脂联素以 Sdhaf1 依赖性方式减轻了缺氧诱导的 OCR 和 ATP 产生减少，而 Sdhaf1 的过表达证实了其足以介导这些影响。重要的是，各种条件下全酶 SDH 的水平与 OCR 相关。我们还表明，脂联素、AMPK、Sdhaf1 以及 SDH 复合体组装的作用都需要 sirtuin 3 (Sirt3)。总之，脂联素通过在心肌细胞中以 AMPK、Sdhaf1 和 Sirt3 依赖的方式促进 SDH 复合物组装来增强线粒体生物能量学。以依赖于 Sdhaf1 的方式，而 Sdhaf1 的过表达证实了其足以调节这些效应。重要的是，各种条件下全酶 SDH 的水平与 OCR 相关。我们还表明，脂联素、AMPK、Sdhaf1 以及 SDH 复合体组装的作用都需要 sirtuin 3 (Sirt3)。总之，脂联素通过在心肌细胞中以 AMPK、Sdhaf1 和 Sirt3 依赖的方式促进 SDH 复合物组装来增强线粒体生物能量学。以依赖于 Sdhaf1 的方式，而 Sdhaf1 的过表达证实了其足以调节这些效应。重要的是，各种条件下全酶 SDH 的水平与 OCR 相关。我们还表明，脂联素、AMPK、Sdhaf1 以及 SDH 复合体组装的作用都需要 sirtuin 3 (Sirt3)。总之，脂联素通过在心肌细胞中以 AMPK、Sdhaf1 和 Sirt3 依赖的方式促进 SDH 复合物组装来增强线粒体生物能量学。