Adiponectin, an adipokine produced and secreted by adipocytes, is involved in regulating the development and progression of insulin resistance, diabetes, and diabetic complications. Heat shock protein 60 (HSP60) is a molecular chaperone, most commonly presenting in mitochondria and participating in the maintenance of protein homeostasis. Accumulating studies have demonstrated that the elevated circulating HSP60 and the decreased intracellular HSP60 are closely associated with diabetic complications such as diabetic cardiomyopathy. However, the underlying mechanism remains poorly understood. In the present study, we reported that HSP60 interacted directly with adiponectin receptors. Its abundance was positively associated with adiponectin action. Furthermore, HSP60 depletion markedly mitigated the protective impacts of adiponectin on high glucose-induced oxidative stress and cell apoptosis in rat cardiac H9c2 cells. In addition, HSP60 knockdown significantly enhanced proteasome activity leading to the degradation of adiponectin receptor 1. Taken together, we showed for the first time that HSP60 interacted with adiponectin receptors and mediated adiponectin signaling through stabilizing adiponectin receptor. This in vitro study also provides an alternative explanation for mechanism by which adiponectin exerts its action. Video abstract.

中文翻译：

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热激蛋白60（HSP60）通过稳定脂联素受体来调节脂联素信号传导。

脂联素是由脂肪细胞产生和分泌的一种脂肪因子，参与调节胰岛素抵抗，糖尿病和糖尿病并发症的发生和发展。热休克蛋白60（HSP60）是分子伴侣，最常见于线粒体中并参与蛋白质稳态的维持。越来越多的研究表明，循环中的HSP60升高和细胞内HSP60降低与糖尿病并发症（如糖尿病性心肌病）密切相关。但是，基本机制仍然知之甚少。在本研究中，我们报道了HSP60与脂联素受体直接相互作用。它的丰度与脂联素的作用正相关。此外，HSP60耗竭显着减轻了脂联素对大鼠心脏H9c2细胞中高葡萄糖诱导的氧化应激和细胞凋亡的保护作用。此外，HSP60敲低显着增强了蛋白酶体活性，导致脂联素受体1降解。总的来说，我们首次证明HSP60与脂联素受体相互作用，并通过稳定脂联素受体介导脂联素信号传导。这项体外研究还为脂联素发挥作用的机制提供了另一种解释。录像摘要。我们首次证明HSP60与脂联素受体相互作用，并通过稳定脂联素受体介导脂联素信号传导。这项体外研究还为脂联素发挥作用的机制提供了另一种解释。录像摘要。我们首次证明HSP60与脂联素受体相互作用，并通过稳定脂联素受体介导脂联素信号传导。这项体外研究还为脂联素发挥作用的机制提供了另一种解释。录像摘要。