Liraglutide Attenuates Hepatocyte Ferroptosis in an In Vitro Model of Metabolic Dysfunction-Associated Steatotic...

This study examined the potential of liraglutide to attenuate ferroptosis in an in vitro model of metabolic dysfunction-associated steatotic liver disease (MASLD). HepG2 cells were allocated into three groups: control (Con), free fatty acid (FFA)-treated, and FFA with liraglutide treatment (FFA+LI). After 48 h of treatment, intracellular triglyceride (TG), glutathione (GSH), malondialdehyde (MDA), and iron levels were quantified using commercially available kits. Superoxide dismutase (SOD) activity was also measured. Lipid accumulation was visualized via Oil Red O staining. Expression of ferroptosis-associated genes was assessed through quantitative RT-PCR and western blotting. FFA treatment induced significant lipid accumulation, elevated TG, MDA, and iron levels, and reduced SOD activity and GSH levels compared to the Con group (all p<0.05). Additionally, FFA exposure increased the expression of TFR1 and downregulated SLC7A11, NRF2, and GPX4 (p<0.05 for all comparisons vs. Con). Liraglutide treatment partially reversed these changes, as evidenced by reduced MDA levels and iron content, downregulation of TFR1, and upregulation of NRF2 and GPX4 (FFA+LI vs. FFA, all p<0.05). Liraglutide demonstrated the ability to mitigate lipid accumulation, oxidative stress, and iron overload in HepG2 cells subjected to FFA-induced injury. These effects were associated with modulation of ferroptosis-related gene expression, suggesting a mechanistic basis for the potential protective role of liraglutide in MASLD. Key words Ferroptosis " Free fatty acid " Liraglutide " Metabolic dysfunction-associated steatotic liver disease " Oxidative stress.