[Animal experiment]-The effect of high-fat diet on insulin resistance and the expression of liver insulin receptor substrates 1 and 2 in Tibet miniature pigs

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

  Method: 10 Tibetan miniature pigs were randomly divided into normal control group (Ctr), 5 animals were fed with normal feed, and IR model (IR model) group, 5 were fed with high-fat feed, and the model was continuously modeled for 12 weeks. After 12 weeks of modeling, weigh and measure body length, calculate body mass index (BMI), take anterior vena cava blood on an empty stomach to determine total cholesterol (TC), low density lipoprotein (LDL-C), high density lipoprotein (HDL) -C), triglycerides (TG), free fatty acids (FFA), fasting blood glucose (FBG) and insulin (insulin), calculate the homeostasis model assessment-estimated insulin resistance (HOMA-IR); simultaneously perform glucose tolerance Test, and calculate the area under the glucose tolerance curve (AUC); take liver tissue to detect IRS-1 and IRS-2 gene and protein expression, and oil red O, PAS and HE staining to observe liver lipid deposition, glycogen and tissue respectively Pathological changes.

  Results: Compared with the normal control group, the weight, BMI index, TC, LDL-C, HDL-C, FFA, FBG, insulin and HOMA-IR indexes of the IR model group were significantly increased (P<0.05, P<0.01); Glucose tolerance test showed that the curve of blood glucose and insulin levels was delayed, while AUC blood glucose and AUC insulin were significantly increased (P<0.05, P<0.01); lipid deposits, increased glycogen, and local liver cell turbidity appeared in liver tissues, Part of the nucleus disappeared or was squeezed to one end, occasionally lymphocyte infiltration; at the same time, the expression of IRS-1 and IRS-2 mRNA and protein in liver tissue were significantly reduced (P<0.05, P<0.01).

  Conclusion: High-fat diet can cause insulin resistance in Tibetan miniature pigs. 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 of Tibetan miniature pigs.