The Effect Of Sleeve Gastrectomy On Fatty Liver In PCOS Rats And Its Mechanism

Objectives The purpose of this study is to prove whether sleeve gastrectomy(SG)can improve fatty liver with polycystic ovary syndrome(PCOS)and obese PCOS,and to explore the mechanism of its effect on liver metabolism.Methods In the preliminary experiment,SD female rats were randomly divided into groups,subcutaneously injected dehydroepiandrosterone(DHEA)to construct a PCOS model,and a 60% high-fat feeding group was set up,while the control group was injected with solvent tea oil,and then SG and sham operation were performed.Namely6 groups: control+sham operation,control+SG,DHEA+sham operation,DHEA+SG,DH+sham operation,DH+SG(DH,DHEA+60% HFD),then compare the weight before and after the operation,estrous cycle,glucose tolerance,Insulin tolerance test and hormone changes.In this experiment,the rat liver obtained in the early stage was frozen sectioned and stained with Oil Red O.After the liver m RNA was extracted,the q PCR of the genes related to glucose metabolism,lipid metabolism,and reproductive metabolism was performed.After the liver protein was extracted,the glucose metabolism,lipid metabolism,and reproductive metabolism related genes were performed.Western blot of pathway proteins.Results The oil red O staining of the liver showed that the lipid droplets stained by PCOS and obese PCOS oil red O were significantly increased,indicating that fatty liver occurred,and after the SG weight loss surgery,the lipid droplets were reduced and the fatty liver was alleviated.According to our q PCR and WB results,the lipid metabolism regulator of liver lipid metabolism,cholesterol regulatory element binding protein 1c(Srebp1c),peroxisome proliferation-activated receptor γ(PPARγ),and peroxisome proliferation-activated receptor α(PPARα),carbohydrate regulatory element binding protein(Ch REBP)genes;fatty acid-related farnesoid X receptor α(FXRα)and farnesoid X receptor β(FXRβ)genes related to fatty acid uptake in the liver;fat de novo synthesis pathway m TOR-AKT2-Insig2-Srebp1c-ACC/FAS in mammalian target of rapamycin(m TOR),acetyl-coenzyme a carboxylase(ACC)protein phosphorylation level,insulin-inducible gene 2(Insig2),Srebp1,serine/threonine protein kinase 2(AKT2)protein,and fatty acid synthase(FAS),an enzyme that synthesizes fatty acids;when lipids are exported from hepatic lipid metabolism,related autophagy is related Apoptosis signal-regulated kinase 1(ASK1)and silent information regulator 1(SIRT1)genes have varying degrees of fatty liver changes in the PCOS and obese PCOS groups,and the fatty liver changes after SG have improved.In the PCOS and obese PCOS groups,hepatic insulin resistance increased,the insulin resistance index(HOMA-IR)increased,and there was a downward trend after SG compared to before surgery.Insulin works through the IR-IRS-PI3K-AKT-m TOR pathway to lower blood sugar and provide energy for the body.Among them,insulin receptor substrate 1(IRS1),insulin receptor substrate 2(IRS2),phosphoinositide 3-kinase(PI3K)protein and silk/threonine protein kinase(AKT)protein have increased phosphorylation levels;The key enzymes of gluconeogenesis,glucose-6-phosphatase(G6Pase),liver pyruvate kinase(L-PK)gene expression decreased;q PCR and WB results show that the liver produces sex hormone binding globulin(SHBG)that can bind to sex hormones)Expression increased significantly after SG surgery in the PCOS and obese PCOS groups.SG may improve the fatty liver of PCOS through a complex network mechanism between lipid metabolism,sugar metabolism,and reproductive metabolism,which may require adenylate-activated protein kinase(AMPK)and extracellular signal-regulated kinase 1/2(ERK1/2)and transcription factor hepatocyte nuclear factor 4α(HNF4α)these three intermediate proteins also have changes that inhibit adipogenesis.Conclusions SG bariatric surgery can improve the fatty liver of PCOS and obese PCOS.The mechanism of improving fatty liver may be related to the lipid metabolism pathway m TOR-AKT2-Insig2-Srebp1-ACC/FAS,the glucose metabolism pathway IRS-PI3K-AKT-m TOR and Sex hormone binding globulin SHBG and other related,the three metabolisms may also be indirectly affected by ERK1/2 MAPK,HNF4α and AMPK,and jointly regulate and improve the fatty liver of PCOS and obese PCOS after SG surgery.