Effects Of Leptin On Glucose Metabolism In CRP Gene Knockout Rats With Polycystic Ovary Syndrome

Objective: To explore the effect of leptin on glucose metabolism in CRP knockout polycystic ovary syndrome model rats.Methods: The heterozygous female rats and the heterozygous male rats were used for mating,and the obtained female wild-type rats and female homozygous rats were used for experiments.Female 4-week-old wild-type rats and CRP KO rats were selected and given with subcutaneous injection of dehydroepiandrosterone,and they were fed with ordinary or high-fat diets,respectively.The modeling time was 12 weeks.Measure the weight,food intake,anal temperature,blood pressure,heart rate,fasting blood glucose,energy metabolism and other indicators of rats.Glucose tolerance(GTT)test and insulin tolerance(ITT)test were used to evaluate rat insulin resistance.The rats with successful modeling were subjected to the extended euglycemic-hyperinsulinemic clamp experiment of infusion of leptin intravenously or third ventricle,and the changes of glucose metabolism in each group were rated.Finally,the acute insulin resistance model of PCOS model rats was established by peripheral infusion of lipids.At the same time,leptin was infused intravenously or intraventricularly,and the extended euglycemic-hyperinsulinemic clamp experiment was performed to evaluate the changes of glucose metabolism.Results: Compared with the ND-DHEA-WT group,the anal temperature,oxygen consumption(VO2)and carbon dioxide production(VCO2)of the ND-DHEA-CRP KO group were significantly increased(P<0.05),and the respiratory exchange rate(RER)Significantly decreased(P<0.05).Compared with the HFD-DHEA-WT group,the body weight,blood pressure,and respiratory exchange rate(RER)of the HFD-DHEA-CRP KO group decreased significantly(P <0.05),anal temperature,oxygen consumption(VO2),and carbon dioxide production(VCO2)was significantly increased(P <0.05).In the glucose tolerance(GTT)test and insulin tolerance(ITT)test,compared with the ND-DHEA-WT group,the GTT-AUC and ITT-AUC of the ND-DHEA-CRP KO group decreased(P<0.05);compared with the HFD-DHEA-WT group,the HFD-DHEA-CRP KO group The GTT-AUC and ITT-AUC decreased(P <0.01).In the peripheral leptin infusion-euglycemic-hyperinsulinemic clamp,compared with the ND-DHEA-WT group,the GIR,GRD,and glycogen inhibition rates of the ND-DHEA-CRP KO group were significantly increased(P <0.05),and HGP was significantly decreased(P <0.05).Compared with the HFDDHEA-WT group,the HFD-DHEA-CRP KO group had significantly higher GIR,GRD,and glycogen inhibition rates(P <0.05 or P <0.01),while HGP decreased significantly(P <0.05).In the peripheral leptin infusion-lipid perfusion-euglycemic-hyperinsulinemic clamp,compared with the NDDHEA-WT group,the GIR,GRD,and glycogen inhibition rates of the NDDHEA-CRP KO group increased significantly(P <0.05 or P <0.01),and HGP decreased significantly(P <0.05).In the central leptin infusioneuglycemic-hyperinsulinemic clamp,compared with the ND-DHEA-WT group,the GIR and glycogen inhibition rates of the ND-DHEA-CRP KO group increased significantly(P <0.05),and HGP decreased significantly(P<0.05).Compared with the HFD-DHEA-WT group,the HFD-DHEA-CRP KO group had significantly higher GIR,GRD,and glycogen inhibition rates(P <0.05 or P <0.01),while HGP decreased significantly(P <0.05).In the central leptin infusion-lipid perfusion-euglycemic-hyperinsulinemic clamp,compared with the ND-DHEA-WT group,the GIR,GRD,and glycogen inhibition rates of the ND-DHEA-CRP KO group increased significantly(P<0.05 or P <0.01),and HGP decreased significantly(P <0.05).Conclusion: In the PCOS model,CRP knockout rats have higher insulin sensitivity than wild-type rats.Under the condition of CRP gene knockout,leptin can improve the glucose metabolism of polycystic ovary syndrome rats better.