GLP-1 Receptor Agonist Liraglutide Modulates the Oxidative Stress and SIRT1/PGC1 Alpha Levels on Liver Tissue in Ovariectomized Rats

Authors : Hale Sayan Özaçmak, Sefa Özduran, Mete Keçeci, Taner Bayraktaroğlu

Pages : 9-18

View : 58 | Download : 41

Publication Date : 2025-04-30

Article Type : Research Paper

Abstract :Aim: Non-alcoholic fatty liver disease (NAFLD), characterized by increased hepatic lipid accumulation, inflammation, and oxidative stress, is the most prevalent liver disease worldwide. Menopause is associated with an increased risk of developing NAFLD. The glucagon-like peptide-1 (GLP-1) receptor is present on human hepatocytes, and GLP-1 receptor agonists have a protective effect against liver steatosis and inflammation. Sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor-α (PPAR-α) are key regulators of hepatic lipid metabolism. This study aimed to determine whether liraglutide exerts a protective effect on the liver of ovariectomized rats through the SIRT1/PGC-1α pathway. Materials and Methods: Ovariectomized (OVX) rats were divided into two groups: a control group and a liraglutide-treated group. Liraglutide treatment lasted for five days at a dose of 150 µg/kg/day. Five days after litaglutid treatment, SIRT1 and PGC-1α levels, along with oxidative stress markers, were analyzed in the liver. SIRT1 and PGC-1α levels were measured using the ELISA method, while malondialdehyde (MDA), a marker of lipid peroxidation, and reduced glutathione (GSH) level were quantified spectrophotometrically. Additionally, liver tissues collected from the animals were stained with hematoxylin and eosin and evaluated histopathologically Results: In ovariectomized rats, decreased levels of SIRT1 and PGC-1α, along with microvesicular steatosis in liver tissue, apoptotic cellular changes, and heightened oxidative stress were observed (p=0.014). Conversely, in the liraglutide-treated groups, SIRT1 and PGC-1α levels were elevated compared to those in the OVX group, and histological changes showed improvement alongside reduced oxidative stress (p=0.036, p=0.05, respectively). Conclusion: This study suggests that fat metabolism is compromised in ovariectomized rats and that liraglutide treatment may confer protection against NAFLD by upregulating SIRT1 and PGC-1α expression in the liver and reducing oxidative stress.
Keywords : Liraglutid, Menopoz, Yağlı karaciğer, SIRT1, PGC-1α