【Animal Modeling】-Effect of high-fat diet on insulin resistance and expression of hepatic insulin receptor substrate 1 and 2 in Tibetan miniature pigs

  Objective: To investigate the effect of high-fat diet on insulin resistance (IR) and the expression of hepatic insulin receptor substrate (IRS) 1 and 2 in Tibetan miniature pigs.

  Methods: 10 Tibetan minipigs were randomly divided into normal control group (Ctr), 5 pigs fed with normal diet, and IR model group (IR model) group, 5 pigs were fed with high-fat diet, and the models were continuously established for 12 weeks. After 12 weeks of modeling, the rats were weighed and measured body length, calculated body mass index (BMI). -C), triglyceride (TG), free fatty acid (FFA), fasting blood glucose (FBG) and insulin (insulin), calculate the insulin resistance index (homeostasis model assessment-estimated insulin resistance, HOMA-IR); The area under the glucose tolerance curve (AUC) was calculated; liver tissue was taken to detect the expression of IRS-1 and IRS-2 gene and protein, and oil red O, PAS and HE staining were performed to observe liver lipid deposition, glycogen and tissue respectively. pathological changes.

  Results: Compared with the normal control group, the body weight, BMI index, TC, LDL-C, HDL-C, FFA, FBG, insulin and HOMA-IR index of the IR model group were significantly increased (P<0.05, P<0.01); Glucose tolerance test showed that the blood glucose and insulin level curve decreased slowly, while AUC blood glucose and AUC insulin were significantly increased (P<0.05, P<0.01); lipid deposition, increased glycogen and local hepatocyte opacity, Some nuclei disappeared or were squeezed to one end, and lymphocyte infiltration was occasionally seen. At the same time, the mRNA and protein expressions of IRS-1 and IRS-2 in liver tissue were significantly decreased (P<0.05, P<0.01).

  Conclusion: High-fat diet can induce insulin resistance in Tibetan miniature pigs, and the decreased expression of IRS-1 and IRS-2 in liver tissue is one of the molecular mechanisms that high-fat diet affects insulin sensitivity in Tibetan miniature pigs.