The hypoglycemic drug GLP-1 receptor agonist can ameliorate hepatic steatosis but the mechanism is not clear. Intake of high fructose leads to non-alcoholic fatty liver disease by stimulating lipid synthesis, and β-catenin is the key molecule for realizing GLP-1 function in extrahepatic tissues; with the discovery of GLP-1 receptor in liver, we speculate that β-catenin might mediate GLP-1 receptor agonist on ameliorating hepatic steatosis induced by high fructose. Wistar rats were fed with high fructose diet for 8 weeks and then treated with GLP-1 receptor agonist exenatide for 4 weeks; the changes of lipid synthesis pathway factors, the expression and nuclear translocation of β-catenin, and the hepatic steatosis of the rats were observed. After the intervention of exenatide, the hepatic steatosis induced by high fructose was improved, the nuclear translocation and expression of β-catenin were facilitated, and the mRNA and protein expression of the upstream regulator SREBP-1 and the downstream key enzymes ACC, FAS and SCD-1 of de novo lipogenesis were down-regulated. GLP-1 receptor agonist may ameliorate hepatic steatosis induced by high fructose by β-catenin regulating de novo lipogenesis pathway. GLP-1 receptor agonist may be a potential new drug for the treatment of non-alcoholic fatty liver disease, and the β-catenin may be an important target for the drug therapy.

降糖药GLP-1受体激动剂可改善肝脂肪变性，但机制尚不清楚。高果糖的摄入会通过刺激脂质合成而导致非酒精性脂肪肝疾病，而β-catenin是在肝外组织中实现GLP-1功能的关键分子。随着肝脏中GLP-1受体的发现，我们推测β-catenin可能介导GLP-1受体激动剂减轻高果糖引起的肝脂肪变性。Wistar大鼠高果糖饮食喂养8周，然后用GLP-1受体激动剂艾塞那肽治疗4周。观察脂质合成途径因子的变化，β-catenin的表达和核易位以及肝脂肪变性。艾塞那肽干预后，高果糖引起的肝脂肪变性得到改善，从头脂肪形成被下调。GLP-1受体激动剂可能通过β-catenin调节从新脂形成途径减轻高果糖引起的肝脂肪变性。GLP-1受体激动剂可能是治疗非酒精性脂肪肝的潜在新药，而β-catenin可能成为药物治疗的重要靶标。