Oleacein prevents metabolic dysfunction-associated hepatic steatosis and dyslipidaemia in ApoE-KO mice

The modification of cardiometabolic risk factors is a major strategy to prevent metabolic dysfunction-associated fatty liver disease (MAFLD), given the current lack of approved pharmacological treatments. This study investigated whether oleacein (OLEA), a key polyphenol in olive oil, can prevent dyslipidemia and hepatic steatosis in apolipoprotein E knockout (ApoE-KO) mice, a model of atherosclerosis and metabolic disturbance. C57BL/6J wild-type (WT, n = 16) and ApoE-KO (n = 16) mice were assigned to four groups (n = 8) and fed for 10 weeks: WT mice received either a standard diet (WT + STD) or an atherogenic diet (WT + ATD), while ApoE-KO mice received the atherogenic diet without (ApoE-KO + ATD) or with OLEA supplementation (50 mg kg^-1 day^-1, oral; ApoE-KO + ATD + OLEA). Metabolic parameters, serum lipid profile, and hepatic triglyceride (TG) content were determined, alongside markers of liver injury, oxidative status (SOD expression and activity), and lipid metabolism (including SCD1 expression). OLEA supplementation significantly improved the serum lipid profile and reduced hepatic TG accumulation (p < 0.05), effects associated with marked downregulation of hepatic SCD1, indicating inhibition of de novo lipogenesis, FABP1 and CPT1. In addition, OLEA restored hepatic SOD1 and SOD2 expression and enhanced serum SOD activity, suggesting reinforcement of antioxidant defenses. Overall, OLEA exerted strong anti-dyslipidemic and hepatoprotective effects in ApoE-KO mice, likely through the combined modulation of lipid synthesis and redox homeostasis. These findings highlight the potential of OLEA as a promising natural compound for preventing diet-induced metabolic and hepatic disorders associated with MAFLD.