Glucagon-like peptide-1 receptor agonist prevented the progression of hepatocellular carcinoma in a mouse model of nonalcoholic steatohepatitis

Motoyasu Kojima, Hirokazu Takahashi, Takuya Kuwashiro, Kenichi Tanaka, Hitoe Mori, Iwata Ozaki, Yoichiro Kitajima, Yayoi Matsuda, Kenji Ashida, Yuichiro Eguchi, Keizo Anzai

Research output: Contribution to journalArticle

Abstract

Glucagon-like peptide-1 (GLP-1) receptor agonists are used to treat diabetes, but their effects on nonalcoholic steatohepatitis (NASH) and the development of hepatocellular carcinoma (HCC) remain unclear. In this study, mice with streptozotocin-and high-fat diet-induced diabetes and NASH were subcutaneously treated with liraglutide or saline (control) for 14 weeks. Glycemic control, hepatocarcinogenesis, and liver histology were compared between the groups. Fasting blood glucose levels were significantly lower in the liraglutide group than in the control group (210.0 ± 17.3 mg/dL vs. 601.8 ± 123.6 mg/dL), and fasting insulin levels were significantly increased by liraglutide (0.18 ± 0.06 ng/mL vs. 0.09 ± 0.03 ng/mL). Liraglutide completely suppressed hepatocarcinogenesis, whereas HCC was observed in all control mice (average tumor count, 5.5 ± 3.87; average tumor size, 8.1 ± 5.0 mm). Liraglutide significantly ameliorated steatosis, inflammation, and hepatocyte ballooning of non-tumorous lesions in the liver compared with the control findings, and insulin-positive β-cells were observed in the pancreas in liraglutide-treated mice but not in control mice. In conclusion, liraglutide ameliorated NASH and suppressed hepatocarcinogenesis in diabetic mice. GLP-1 receptor agonists can be used to improve the hepatic outcome of diabetes.

Original languageEnglish
Article number5722
Pages (from-to)1-13
Number of pages13
JournalInternational journal of molecular sciences
Volume21
Issue number16
DOIs
Publication statusPublished - Aug 2 2020

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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    Kojima, M., Takahashi, H., Kuwashiro, T., Tanaka, K., Mori, H., Ozaki, I., Kitajima, Y., Matsuda, Y., Ashida, K., Eguchi, Y., & Anzai, K. (2020). Glucagon-like peptide-1 receptor agonist prevented the progression of hepatocellular carcinoma in a mouse model of nonalcoholic steatohepatitis. International journal of molecular sciences, 21(16), 1-13. [5722]. https://doi.org/10.3390/ijms21165722