Krill Oil Attenuates Acute Alcohol‐Induced Liver Injury by Remodeling Mitochondrial Dynamics and Metabolic Restoration

Alcohol consumption is a primary etiological factor in liver disease. Although krill oil (KO) exhibited hepatoprotective effects against alcohol‐induced liver injury, its mechanisms were undefined. This study elucidated the protective role of KO in a murine model of acute alcohol‐induced liver injury (AALI) via intragastric ethanol administration, followed by histopathological, biochemical, and metabolomics analyses. Results demonstrated that KO dose‐dependently ameliorated hepatic damage, evidenced by elevated alcohol dehydrogenase activity and reductions in serum alanine aminotransferase, aspartate aminotransferase, and triglyceride levels. Nontargeted metabolomics identified mitochondrial dysfunction as the central perturbation. Mechanistically, KO significantly reversed alcohol‐induced mitochondrial dysfunction. It restored the activity of electron transport chain complexes I–V, thereby recovering mitochondrial membrane potential and ATP production. This functional recovery may be attributed to the remodeling of mitochondrial dynamics, characterized by enhanced MFN2 and OPA1 regulation and reduced DRP1 regulation, together with the reactivation of the AMPK/PPARα signaling pathway. Consequently, this restoration enhanced fatty acid oxidation and reduced ROS generation, strengthening antioxidant defenses. These results collectively suggested that KO provides significant protection against AALI by restoring mitochondrial homeostasis, thereby modulating lipid metabolism and reducing oxidative stress. This research indicated the potential of KO as a valuable dietary strategy for managing alcohol‐induced liver damage.