Modified Dachaihu Decoction Regulates FOXO3a Acetylation Activated Autophagy and Relieving Insulin Resistance in Obesity

Cong Long, Yang Gao, Xuke Han, Su-qin Li, Qiu Chen
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Abstract

Background The previous studies of our research group indicate that the weakening of mitochondrial autophagy function is the key mechanism of obesity-induced insulin resistance, and Mitochondrial autophagy mediated by PINK1/Parkin pathway can reverse mitochondrial dysfunction. Recently, we found that FOXO3a, as an upstream regulator of PINK1, has been found to play a key role in regulating mitochondrial autophagy.However,FOXO3a is regulated by deacetylation. Objective To explore whether Modified Dachaihu Decoction can regulate liver mitochondrial autophagy mediated by the PINK1/Parkin signal pathway by regulating the expression of FOXO3a acetylation. Western blot showed that compared with the model control group, the expression of mitochondrial autophagy-related proteins and FOXO3a in the Modified Dachaihu Decoction group increased, and the expression of ace-FOXO3a decreased (P < 0.05). We speculate that in this experiment, Modified Dachaihu Decoction may regulate mitochondrial autophagy mediated by PINK1/ Parkin signal pathway by downregulating the expression of FOXO3a acetylation, to reduce Hepatic Insulin Resistance in Obesity.
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大柴胡汤加味调节肥胖FOXO3a乙酰化激活的自噬,缓解胰岛素抵抗
背景本课题组先前的研究表明,线粒体自噬功能的减弱是肥胖诱导胰岛素抵抗的关键机制,PINK1/Parkin通路介导的线粒体自噬可以逆转线粒体功能障碍。最近,我们发现FOXO3a作为PINK1的上游调节因子,在调节线粒体自噬中发挥着关键作用。然而,FOXO3a是通过脱乙酰基来调节的。目的探讨大柴胡汤是否能通过调节FOXO3a乙酰化的表达,调节PINK1/Parkin信号通路介导的肝线粒体自噬。Western blot结果显示,与模型对照组相比,大柴胡汤组线粒体自噬相关蛋白和FOXO3a的表达增加,ace-FOXO3a表达降低(P<0.05),大柴胡汤可通过下调FOXO3a乙酰化的表达,调节PINK1/Parkin信号通路介导的线粒体自噬,降低肥胖患者的肝胰岛素抵抗。
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