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.
Methods: Establish cell models. They were divided into three groups (blank control group, model control group, and Modified Dachaihu Decoction group). The supernatant was extracted and determined by a biochemical method; The insulin sensitivity of each group was evaluated by a 3H-D-glucose incorporation test; MDA and TNFα、IL-6 in the supernatant were detected by ELISA level; The level of SOD was detected by spectrophotometry.The expression of mitochondrial autophagy-related proteins and the expression of FOXO3a and ace-FOXO3a were measured by Western blot.
Results: Compared with the model control group, the Modified Dachaihu Decoction group increased insulin sensitivity, and The levels of TNF- α、IL-6, and MDA decreased, while the activity of SOD increased (P < 0.05). 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).
Conclusions: 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.
Keywords
FOXO3a Acetylation, Autophagy, Hepatic Insulin Resistance