益气化浊汤调控lnc-PID1及PID1/IRS-1/FoxO1通路改善2型糖尿病肝脏异位脂质沉积的作用机制OA

Objective:To explore the efficacy and mechanism of Yiqi Huazhuo Decoction(YD)in ameliorating hepatic ectopic lipid deposition(ELD)and insulin resistance(IR)in type 2 diabetes mellitus(T2DM)rats.Methods:ZDF rats were fed a high-sugar and high-fat diet to establish a T2DM model,and divided into normal,model,low/high-dose YD and metformin groups.After 8 week intervention,glycolipid metabolism,hepatic fat deposition and gene/protein expression were detected,with differentially expressed lncRNA/mRNA screened by RNA-seq.IR model of BRL-3A cells was established,and the interaction between lnc-PID1 and PID1 was verified via siRNA interference and RIP-qPCR.Results:YD significantly reduced glycolipid levels,improved IR,alleviated liver injury and ELD(P＜0.05),down-regulated lnc-PID1/PID1,activated IRS-1/Akt and inhibited FoxO1(P＜0.05).Cell experiments suggested siRNA inhibiting lnc-PIDl enhanced IR cell glucose consumption and confirmed lnc-PID1-PID1 interaction(P＜0.05).Conclusion:YD improves hepatic IR and ELD by inhibiting lnc-PID1/PID1,activating the IRS-1/Akt pathway and suppressing FoxO1 activity.