Glucagon-Like Peptide-1 Receptor Agonist Prevented the Progression of Hepatocellular Carcinoma in a Mouse Model of Nonalcoholic Steatohepatitis

• Published in: International journal of molecular sciences 2020-08, Vol.21 (16), p.5722
• Main Authors: Kojima, Motoyasu, Takahashi, Hirokazu, Kuwashiro, Takuya, Tanaka, Kenichi, Mori, Hitoe, Ozaki, Iwata, Kitajima, Yoichiro, Matsuda, Yayoi, Ashida, Kenji, Eguchi, Yuichiro, Anzai, Keizo
• Format: Article
• Language: English
• Subjects: Agonists; Animals; ballooning; Beta cells; Blood glucose; Blood Glucose - analysis; Carcinogenesis - drug effects; Carcinoma, Hepatocellular - prevention & control; Diabetes mellitus; Diabetes Mellitus, Experimental - chemically induced; Diabetes Mellitus, Experimental - complications; Diabetes Mellitus, Experimental - drug therapy; Diet, High-Fat - adverse effects; Disease Models, Animal; Fasting; GLP-1 receptor agonists; Glucagon; Glucagon-like peptide 1; Glucagon-Like Peptide-1 Receptor - agonists; hepatocarcinogenesis; Hepatocellular carcinoma; High fat diet; Histology; Hypoglycemic Agents - administration & dosage; Insulin; Insulin - blood; Insulin resistance; islet; Kinases; liraglutide; Liraglutide - administration & dosage; Liver; Liver cancer; Liver Neoplasms - prevention & control; Male; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease - complications; Non-alcoholic Fatty Liver Disease - drug therapy; Non-alcoholic Fatty Liver Disease - etiology; Obesity; Pancreas; prognosis; Steatosis; Streptozocin; Streptozocin - adverse effects; Treatment Outcome; Tumors; β-cell
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21165722

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.