β-catenin mediates the effect of GLP-1 receptor agonist on ameliorating hepatic steatosis induced by high fructose diet

  • Zhe Gao Department of Internal Medicine, Hebei Medical University; Department of Endocrinology, Hebei General Hospital, Shijiazhuang, China.
  • Guang-Yao Song | sguangyao@163.com Department of Internal Medicine, Hebei Medical University; Department of Endocrinology, Hebei General Hospital, Shijiazhuang, China.
  • Lu-Ping Ren Department of Endocrinology, Hebei General Hospital, Shijiazhuang, China.
  • Hui-Juan Ma Department of Endocrinology, Hebei General Hospital, Shijiazhuang, China.
  • Bo-Qing Ma Department of Endocrinology, Hebei General Hospital, Shijiazhuang, China.
  • Shu-Chun Chen Department of Endocrinology, Hebei General Hospital, Shijiazhuang, China.

Abstract

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.

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Published
2020-09-15
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Ethics Approval
The study was approved by the Animal Ethics Committee of Hebei General Hospital
Keywords:
Fructose, hepatic steatosis, GLP-1 receptor agonist, β-catenin, de novo lipogenesis
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How to Cite
Gao, Z., Song, G.-Y., Ren, L.-P., Ma, H.-J., Ma, B.-Q., & Chen, S.-C. (2020). β-catenin mediates the effect of GLP-1 receptor agonist on ameliorating hepatic steatosis induced by high fructose diet. European Journal of Histochemistry, 64(3). https://doi.org/10.4081/ejh.2020.3160