Liraglutide With Metformin Therapy Ameliorates Hepatic Steatosis and Liver Injury in a Mouse Model of Non-alcoholic Steatohepatitis

• Published in: In vivo (Athens) Vol. 37; no. 3; pp. 1037 - 1046
• Main Authors: CHIU, HONG-YI, TSAI, SHIH-CHANG, TSAI, FUU-JEN, LO, YU-HSIANG, CHENG, CHING-CHANG, LIU, TING-YUAN, JHAN, SYUN-RONG, YANG, JAI-SING, CHIU, YU-JEN
• Format: Journal Article
• Language: English
• Published: Greece International Institute of Anticancer Research 01.05.2023
• Subjects: Alanine Transaminase; Animals; Choline - metabolism; Choline - pharmacology; Choline - therapeutic use; Diabetes; Diet; Disease Models, Animal; Enzymes; Fatty liver; FDA approval; Glucagon; Insulin resistance; Laboratory animals; Liraglutide - metabolism; Liraglutide - pharmacology; Liraglutide - therapeutic use; Liver - pathology; Liver cirrhosis; Metabolism; Metformin - pharmacology; Methionine - metabolism; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease - drug therapy; Non-alcoholic Fatty Liver Disease - etiology; Non-alcoholic Fatty Liver Disease - metabolism; Obesity; Variance analysis; Weight control; United States > US; MCD diet; metformin; liver injury; C57BL/6JNarl mouse model; Liraglutide; non-alcoholic steatohepatitis
• ISSN: 0258-851X; 1791-7549; 1791-7549
• DOI: 10.21873/invivo.13178

Non-alcoholic fatty liver disease is a major cause of liver-related morbidity and mortality. Metformin is a widely used medication and may have additional benefits beyond glycemic control. Liraglutide, a novel treatment for diabetes and obesity, also has beneficial effects on non-alcoholic steatohepatitis (NASH). Metformin and liraglutide have both benefited NASH treatment. However, no study has reported the effects of combination therapy with liraglutide and metformin on NASH. We investigated the in vivo effects of metformin and liraglutide on NASH in a methionine/choline-deficient (MCD) diet-fed C57BL/6JNarl mouse model. Serum triglyceride, alanine aminotransferase and alanine aminotransferase levels were documented. Histological analysis was performed according to the NASH activity grade. After treatment with liraglutide and metformin, body weight loss improved, and the liver/body weight ratio decreased. The metabolic effects and liver injury improved. Liraglutide and metformin alleviated MCD-induced hepatic steatosis and injury. Histological analysis revealed that NASH activity was reduced. Our results provide evidence for the anti-NASH activity of liraglutide in combination with metformin. Liraglutide with metformin may offer the potential for a disease-modifying intervention for NASH.