COMPARATIVE STUDY ON THE EFFECT OF PLIN1 GENE KNOCKOUT ON INSULIN RESISTANCE IN MICE
Objective To compare the effects of high-fat diet,high-fat diet combined with intraperitoneal injection of streptozotocin(STZ),plin1 gene knockout(plin1-/-)and plin1 gene knockout(plin1-/-)plus high-fat diet on insulin resistance in mice.Methods C57BL/6J mice were divided into five groups:normal diet group(W-N),high-fat diet group(W-H),high-fat diet+STZ group(W-S),plin1-/-+normal diet group(K-N),plin1-/-+high-fat diet group(K-H).Each group had eight rats and was fed for 12 weeks.The body weight,fasting blood glucose(FBG),glucose tolerance(GTT)and insulin tolerance(ITT)were measured and the areas under the curve(AUC)of GTT and ITT were calculated.The mice were sacrificed after 12 weeks,and the serum and adipose tissue were collected.Fasting serum insulin(FINS),serum triglyceride(TG)and free fatty acids(FFA)were measured and homeostasis model assessment of insulin resistance(HOMA-IR)was calculated.The protein expression levels of phosphatidylinositol 3 kinase(PI3K),protein kinase B(AKT)and glucose transporter 4(GLUT4)in adipose tissue were detected by Western blotting.Results Compared with the W-N group,the FBG,AUC of GTT and ITT,HOMA-IR,serum TG in the mice from other four groups were significantly increased,and the protein expressions of PI3K,p-AKT and GLUT4 were significantly decreased(P<0.05).The body weight of the W-H group was significantly increased(P<0.05),and that of the K-N group was significantly decreased(P<0.05).FINS was significantly elevated in the K-N,K-H and W-S groups(P<0.05),and FFA was significantly increased in the W-H group but reduced in the K-N group(P<0.05).Compared with the K-N group,the body weight of the W-H group,K-H group and W-S group was significantly increased(P<0.05).Serum FFA was significantly higher(P<0.05)in the W-H group.In the W-S group,FBG was significantly elevated and PI3K protein expression was dramatically downregulated(P<0.05).The AUC of GTT and ITT,HOMA-IR,serum TG and FFA in the K-H and W-S groups were significantly increased,and the protein expressions of p-AKT and GLUT4 were significantly decreased(P<0.05).There were no significant changes in FBG,AUC of GTT and ITT,FINS,HOMA-IR,TG,and the protein expressions of PI3K,p-AKT and GLUT4 in the W-H group.Conclusion The change of IR induced by plin1-/-is equivalent to that induced by high-fat diet,but lower than that induced by high-fat diet+STZ.The changes of IR in plin1-/-mice fed with the high-fat diet is higher than in plin1-/-mice fed the normal diet.[ACTA NUTRIMENTA SINICA,2024,46(2):171-176]
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