Abstract: Objective: To investigate the effects of Exendin-4 (Ex-4) on the expressions of lipid metabolism related genes in the human liver cancer HepG₂ cells with insulin resistance (IR), and to elucidate the effect of Ex-4 in improvement of IR. Methods: The HepG₂ cells in logarithmic growth phase were induced into IR model with high concentration of insulin, then divided into control group (HepG₂ cells), IR group (HepG₂ cells were treated with insulin,HepG₂-IR cells), and Ex-4 group (HepG₂-IR cells were treated with Ex-4). Glucose oxidase (GOD-POD) kit was used to detect the consumption of glucose.The cell morphology and intracellular lipid drip formation were observed by Oil red O staining. The triglyceride (TG) level in cells was detected by kit; qRT-PCR was used to detect the mRNA expression levels of acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), sterol regulatory element-binding protein-1c (SREBP-1c) and apolipoprotein B100 (apoB100). Results: Compared with control group(HepG₂ cells), the glucose consumption in the HepG₂-IR cells in IR group was significantly decreased (P<0.01). Compared with IR group, the glucose consumption in the HepG₂-IR cells in Ex-4 group was increased (P<0.05). The Oil O red staining results showed that compared with control group, the fat percentage in the HepG₂-IR cells in IR group was increased(P<0.05); compared with IR group, the fat percentage in Ex-4 group was decreased (P<0.05). Compared with control group, the level of TG in the cells in IR group was significantly increased (P<0.01); compared with IR group, the level of TG in the cells in Ex-4 group was significantly decreased (P<0.05).The qT-PCR results showed that compared with control group, the expression levels of ACC FAS and SREBP-1c mRNA in the cells in IR group were increased (P<0.01), and the expression level of apoB100 mRNA was decreased (P<0.05); compared with IR group, the expression levels of ACC, FAS and SREBP-1c mRNA in the cells in Ex-4 group were decreased (P<0.05),and the expression level of apoB100 mRNA was increased (P<0.01). Conclusion: Ex-4 can regulate the expressions of lipid metabolism related genes in the HepG₂ cells and improve IR.

Key words: HepG₂ cells, insulin resistance, lipid metabolism, Exendin-4, acetyl-CoA carboxylase, fatty acid synthase