measurement of serum level for SOD,MDA, and TFR-1(ELIZA), gene expression of SLC7A11, immunohistochemistry for GPX4,NRF2, and HO-1, and serum iron (spectrophotometry).

Obesity, a multifaceted metabolic condition, is linked to oxidative stress and disrupted redox homeostasis, leading to ferroptosis and metabolic dysfunction. This study sought to examine the modulatory effects of the GLP-1 receptor agonist liraglutide on oxidative stress and ferroptosis-related indicators in obese rats produced by a high-fat diet (HFD). Thirty-five male Wistar rats were randomly allocated into five groups: a control group, a high-fat diet-induced obesity group, and three liraglutide treatment groups (100, 200, and 400 μg/kg/day). Following a 4-week induction of a high-fat diet, liraglutide was delivered subcutaneously for a duration of 28 days. Body weight and Lee index were assessed to evaluate metabolic status. Gene expression of SLC7A11 and immunohistochemical expression of NRF2, HO-1, and GPX4 in hepatic tissues were measured to assess redox and ferroptotic changes. HFD significantly increased body weight and reduced the expression of antioxidant and ferroptosis-regulatory markers. Liraglutide treatment, particularly at high doses, significantly reversed these effects by upregulating SLC7A11 gene expression and enhancing NRF2, HO-1, and GPX4 protein expression in a dose-dependent manner. These findings suggest that liraglutide restores antioxidant capacity and inhibits ferroptosis via activation of the SLC7A11/NRF2/HO-1/GPX4 axis. Beyond its metabolic benefits, liraglutide may exert cytoprotective effects, highlighting its potential therapeutic role in obesity-associated oxidative stress and ferroptotic injury.