The expression of chemerin and the influence of sitagliptin on its expression in non-alcoholic fatty liver disease rats complicated with prediabetes

Abstract

Objective: To study the role of chemerin in the development and progression of non-alcoholic fatty liver disease (NAFLD) rats complicated with prediabetes and explore the effect of sitagliptin on the expression of chemerin. Methods: The model of NAFLD and prediabetic rats was established. The rats were then randomly divided into normal group, model group and intervention group. Sitagliptin intervention was performed for 8 weeks after 8 weeks's feeding with high-fat diet. After that, the level of blood glucose, insulin and chemerin was measured. Cytological changes of liver, omentum and epididymal adipose tissue were observed by HE staining. The distribution of chemerin in the tissues was observed by immunohistochemistry. The mRNA and protein expression of chemerin and chemokine-like receptor 1 (chemR23) in liver and adipose tissue were detected by RT-PCR and Western blotting. Results: After 8 weeks of sitagliptin treatment, compared with the normal group(n=8), serum chemerin in the model group (n=6) increased[(35.19±3.86) ng/L vs (29.90±2.17) ng/L, P=0.046)]. Serum chemerin in the intervention group (n=6) was lower than that of the normal group[(23.20±1.89) ng/L vs (29.90±2.17) ng/L, P=0.013)]. Compared with the normal group, the mRNA and protein expression of chemerin in the liver and omentum adipose tissue of the model group increased (P<0.05). The expression amount of the omental adipose tissue was more than that of the liver(P<0.05). The mRNA expression of chemR23 both in liver and omental adipose tissue increased (P<0.05), and the expression amount of the liver was more than that of omental adipose tissue. The levels of fasting blood glucose[(5.72 ±1.36)mmol/L vs(3.77±0.77)mmol/L, P=0.002], total cholesterol[(1.53±0.09)mmol/L vs (1.23±0.17)mmol/L, P=0.032], aspartate aminotransferase[(319.8±104.4)U/L vs (195.0±25.0) U/L, P=0.016]in the model group were significantly higher than those in the normal group. The differences between the intervention group and the normal group was not significant. But the level of fasting blood glucose[(4.33±0.39)mmol/L vs (5.72±1.36)mmol/L, P=0.019], total cholesterol[(1.23±0.17)mmol/L vs (1.53±0.09)mmol/L, P=0.047]and aspartate aminotransferase[(198.4±22.8)U/L vs (319.8±104.4)U/L, P=0.014)]of the intervention group was significantly lower than those of the model group. Conclusions: Increasing expression of serum chemerin is consistent with hepatic steatosis, suggesting that chemerin can serve as a serological warning indicator for NAFLD complicated with pre-diabetes. Sitagliptin affects the mRNA and protein expression of chemerin and its receptor chemR23 in steatosis liver. This may provide a research direction for the pathophysiology and treatment of NAFLD.