The Effect Of Exenatide On Nonalcoholic Fatty Liver Disease Induced By High-fat Diet In Rats

Objective:1. To observe the effect of Exenatide on nonalcoholic fatty liver disease (NAFLD) rats induced by high-fat feeding.2. To research the molecular mechanism of Exenatide on NAFLD.Methods:1. Twenty-three Sprague-Dawley (SD) rats were randomly divided into three groups of NC group (normal control, 8rats), HF group (treated with high-fat diet, 7rats) and HF+Exe group (treated with high-fat diet plus Exenatide, 8rats). Eight weeks later the HF+Exe group rats were treated with Exenatide by subcutaneous injection with Exenatide (10 g/kg, twice a day) for 8 weeks.2. All rats were killed at sixteenth week, then body and liver weight were calculated and blood FBG, FINS, TC, TG, FFA, HDL-C, LDL-C, ALT, AST were detected. Liver index (liver weight/body weight×100%) and HOMA-IR(FBS×FINS/ 22.5)was calculated.3. Liver TG were measured by Folch method. Histological changes were analyzed with HE, oil red O staining.4. Expressions of SREBP-1c, PPAR , ACC, SCD-1mRNA was analyzed by real-time fluorescence reverse transcription polymerase chain reaction.Results:1. In comparison with NC group, increased rat weight, hepatic index, liver TG, serum FINS, HOMA-IR, TG, FFA, AST, ALT were observed in HF group.2. Body weight, hepatic index, liver TG and serum FINS, HOMA-IR, TG, FFA,TC, LDL-C, ALT in HF+Exe group were significantly lower than that of HF group.3. Histopathology, the hepatic steatosis in HF group was severer than that of the control group (P<0.01). Compared with HF group, the hepatic steatosis was significantly lighten in HF+Exe group (P<0.01).4. Gene expressions of PPAR demonstrated a trend of down-regulation in HF group but significant up-regulation by adding Exenatide (P<0.05). The ACC, SCD-1 mRNA expression revealed a substantial increase in HF group (P<0.01) and retrieved significantly by Exenatide co-administration compared with HF group (P<0.01).Conclusions:1. Exenatide used for 8 weeks possesses potential for a direct lipid-lowering effect on NAFLD along with improvement of metabolic disorder and IR and no low-glucose response. It is suggestive that Exenatide might be effective in treating NAFLD rats induced by high-fat feeding.2. It would be beneficial in the improvement of IR and treatment of NAFLD, possibly via lowering ACC and SCD-1 mRNA expression and increasing the expression of PPAR- mRNA.