Tissue-specific Effects Of Hihg Fat Diet On The Expression Of Genes Involved In Glucose-lipid Metabolism In AopE^-/- Mice

Objective: To establish an insulin resistance (IR) animal model induced by high-fat diet in ApoE^-/- mice and further investigate the effects and possible molecular mechanism on the related genes of glucose-lipid metabolism.Methods: Twenty male ApoE^-/- mice were randomly divided into normal-chow diet group (NC group, n=10) and high-fat diet fed (HFD) group (HF group, n=10) and fed for 16 weeks. Blood samples were collected for measurement of plasma glucose, insulin and lipid levels. Hepatic and adipose tissues were collected for measurement of mRNA and protein levels of glucose-lipid metabolism related genes via real-time PCR and Western-blot, respectively.Results: Fasting blood glucose, plasma insulin, triglyceride, free fatty acids (FFA), total cholesterol, LDL-C and HDL-C were significantly elevated in HF group compared with NC group (all P<0.01). The HMGCR, SREBP-2 and LDLr mRNA expressions of hepatic tissues in HF group were significantly decreased compared with NC group (P<0.05 and P<0.01). In both tissues HFD markedly decreased the mRNA expression of ATGL and PPARγ(P<0.01), in parallel with the decrease of protein levels of ATGL in fat (P<0.01), but HSL mRNA expressions were not significantly changed (P>0.05). FGF-21,β-klotho, FGFR1 and FGFR3 mRNA levels in two tissues were all significantly elevated in HF group, in parallel with the up-regulation of FGF-21 protein levels in both tissues and plasma; FGFR4 mRNA expression was up-regulated in liver but unchanged in fat; FGFR2 mRNA expressions were not significantly changed (P>0.05). In both tissues visfatin mRNA and protein expressions were all lower in HF group than NF group (P<0.01 and P<0.05); Plasma visfatin protein levels were also reduced in HF group (P<0.01); Adiponectin mRNA expressions in adipose tissue were decreased (P<0.01).Conclusion: High-fat diet feeding ApoE^-/- mice display abnormality of glucose-lipid metabolism and insulin resistance; Hyperglycemia, dyslipidosis and hyperinsulinemia in this animal model might result from, at least in part, the changes of these key enzymes and transcription factors.