Background: Nonalcoholic fatty liver disease (NAFLD) is a widespread health issue and is considered the most common liver disease globally. Liraglutide, a glucagon-like peptide-1 receptor agonist, is a promising and innovative drug. Our study aimed to investigate the protective role of liraglutide in experimentally induced NAFLD in the rat model.

Methods: Forty healthy adult male albino rats were used, they were assigned to 3 main groups: Group I (Control) which is subdivided into two equal subgroups, Group II (HFD group) which rats were given HFD for 12 weeks, and Group III (HFD+liraglutide) in which rats were fed with HFD in the same way as group II in concomitant with liraglutide that was injected subcutaneously daily (0.2 mg/kg) for 12 weeks. Blood samples and liver tissues were collected and assayed for biochemical, histological, and immunohistochemical studies.

Results: The HFD group exhibited a significant increase in BMI, AC, serum ALT, AST, and serum lipid profile levels. Additionally, hepatic destructive changes were observed such as hepatocellular vacuolation, apoptosis, and congested blood vessels, along with a significant increase in the area percentage of collagen fibers, caspase 3 immunoreactions, and the number of GFAP immunoreactivity of hepatic stellate cells. These distortions were confirmed by ultrastructural assessment. In contrast, the HFD+liraglutide group exhibited normal BMI, AC, ALT, AST, and lipid profiles with critical preservation of the liver histoarchitecture.

Conclusion: NAFLD significantly affects hepatic biochemical parameters and cytoarchitecture, leading to fibrosis and apoptosis. Liraglutide administration with a high-fat diet can protect the liver from these changes.