Impact of 4-tert-Butylphenol on Inflammation and Glycogen Metabolism in Cyprinus carpio L via the miR-363/PKCδ Axis

4-tert-Butylphenol (4-tBP), widely used in manufacturing polycarbonate plastics and epoxy resins, is commonly found in aquatic environments globally. This study investigates the chronic (60 days) hepatotoxic effects and the underlying mechanism of 4-tBP on fish, including concentrations with environmental relevance (≤100 μg/L), using Cyprinus carpio L. as the model. Results showed that 1–500 μg/L 4-tBP triggered significant alterations in oxidative stress markers (superoxide dismutase (SOD), glutathione peroxidase (GPx), and malondialdehyde (MDA)) and liver enzymes (alanine aminotransferase (ALT) and aspartate aminotransferase (AST)), with a dose–response relationship confirmed by the Integrated Biomarker Response (IBR) index. Histopathological analysis and molecular experiments revealed inflammatory responses, disruptions in glycogen metabolism, and critical insulin signaling pathways (IRS1, AKT, and GSK3β). Further investigations, including miRNA sequencing and in vitro assays in primary hepatocytes, identified the miR-363/PKCδ axis as a critical regulatory pathway affecting these changes. This study demonstrated that chronic, low-level exposure to 4-tBP can induce hepatotoxicity in Cyprinus carpio L. via the miR-363/PKCδ axis. These findings highlight the potential ecological and health risks posed by 4-tBP in the environment and suggest potential targets for therapeutic intervention.