Krill Oil Improves Hepatic Metabolic Dysfunction and Is Associated with Restored ER-Phagy in High-Fat-Diet-Induced MAFLD Mice

Metabolic-dysfunction-associated fatty liver disease (MAFLD) is characterized by hepatic lipid accumulation and metabolic imbalance. This study investigated the effects and mechanisms of krill oil (KO) on MAFLD, focusing on endoplasmic reticulum autophagy (ER-phagy). A high-fat diet-induced MAFLD mouse model was established, followed by an 8-week KO intervention. Histopathology, metabolomics, and biochemical analyses were performed to evaluate the protective effects and underlying mechanisms of KO. Results showed that KO significantly alleviated liver injury, hepatic steatosis, and metabolic disorders in MAFLD mice. Metabolomics analysis revealed that KO remodeled hepatic metabolic profiles by regulating lipid-related pathways. Furthermore, LC3/CANX colocalization analysis demonstrated that KO markedly enhanced ER-phagy in MAFLD livers. Consistently, KO promoted ER-phagy activation and regulated the expression of ER-phagy-associated proteins, including CANX, CKAP4 and the ER-phagy receptor FAM134B. Collectively, KO improves MAFLD by restoring lipid metabolic homeostasis and ER-phagy, providing new insights into its potential as a functional dietary intervention for metabolic liver disorders.