The Effect Of RNAi-Mediated Adiponectin Gene Inhibition On Glucose-Lipid Metabolism In ApoE-/-Mice

Objective: To investigate the effect of RNAi-mediated adiponectin gene silencing on glucose-lipid metabolism in ApoE-/- mice.Methods: Insulin resistance (IR) model was established by feeding a high-fat diet for 16 weeks and injecting adiponectin shRNA adenovirus in ApoE-/- mice. The glucose-lipid metabolism in awake mice were evaluated by hyperinsulinemic-euglycemic clamp technique combined with 3- [3H] glucose as a tracer.Results: The plasma adiponectin level in ApoE-/- mice with high-fat diet and adiponectin shRNA adenovirus injection (ADI group) was significantly lower than that in ApoE-/- mice with high-fat diet only (HF group), normal-chow (NF group) and naked adenovirus injection (GF group) (all P<0.01). Fasting blood glucose (FBG), fasting plasma insulin (PIns), free fatty acids (FFA) , TC, TG, LDL-C, HDL-C and body weight were significantly elevated in three high-fat diet groups compared with in NF group, (P<0.01 ) . However, PIns, FFA, TC, TG, LDL-C and HDL-C in ADI group were significantly higher than the HF(P<0.01) and GF groups (P<0.05). During the steady-state of clamp, plasma insulin was significantly higher in ADI group than HF and NF groups ( both P<0.01). Although FFA, TC and TG were suppressed in all group, they were higher in ADI group than HF and NF groups ( both P<0.01). In ADI group, glucose infusion rate (GIR) was significantly decreased compared with HF and NF groups (both P<0.01). In the end of clamp, glucose disappearance rate (GRd) was significantly lower and HGP significantly higher in ADI group than that in HF and NF groups ( all P<0.01).Conclusion: A typical Pathophysiological phenotype of IR could arise in ApoE-/- mice with long-term high-fat feeding and adiponecting gene silencing.