Role Of Sumoylational Modification Of PPARγ1K77R In Endothelial Insulin Resistance In Rats Induced By High Sucrose And Fat Diet

Objective:The aim of this study is to research the role of sumoylational modification of PPARγ1K77R in high sucrose and fat diet(HSFD)-induced endothelial insulin resistance(IR)in rats by Co-infecting three constructed recombinant adenoviruses.Methods:First,Male SD rats were injected with a low dose streptozotocin(35mg/kg)and fed with diets enriched in sucrose and fat to establish the model of endothelial IR.Then the rats were randomly divided into 4 groups,namely,Control group(Ctrl),IR group,IR with PPARy-free adenovirus group(Vehicle),IR with HA-PPARγ1K77R,Myc-SUMO-1,Flag-PIAS1 recombinant adenovirus group(Ad).After 8 weeks,the following indicators were detected:①the morphological indexes in rats such as Weight,Length,BMI,Fat coefficient;②the levels of fasting plasma glucose,insulin,triglyceride and total cholesterol in serum;③the levels of NO and Ang Ⅱ in serum;④the levels of MDA in serum and the activity of SOD-Mn;⑤the expression levels of PPARγ1K77SUMO-1 in rat thoracic aorta;⑤the expression levels of HA-PPARγ1K77R,Myc-SUMO-1,Flag-PIAS1,pS176-IKKα/β in rat thoracic aorta;⑥the expression levels of PPARyl target genes including PI3K,AKT,eNOS in rat thoracic aorta;⑦ the vascular endothelial dependent relaxant response of rat thoracic aorta;Results:①The levels of fasting plasma glucose,insulin,triglyceride,total cholesterol,MDA,Ang Ⅱ and HOMA-IR in IR group,were significantly higher than those in Ctrl group,but the levels of NO,SOD-Mn were significantly decrease,suggesting establishment of the IR model was successful.②The expression levels of PPARγ1K77-SUMO-1 in rat thoracic aorta in Ad group were remarkely increased,suggesting that the adenovirus Coinfection was successful.③The results also showed that the sumoylational modification of PPARγ1K77R significantly increased the levels of eNOS and NO but reduced the levels of AngⅡwhich suggested sumoylational modification of PPARγ1K77R significantly improves endothelial IR in systemic IR rats.④The results showed that the sumoylational modification of PPARγ1K77R can increased acetylcholine(Ach)-dependent vasodilation response of aorta,which suggested the sumoylational modification of PPARγ1K77R improves significantly the vascular endothelial dependent relaxant response in obese and IR rats.Conclusion:Sumoylational modification of PPARγ1K77R could improve endothelial IR and endothelial dependent relaxant response in obese and IR rats induced by HSFD.