Transcriptomic profiling reveals tetrabromobisphenol A-induced dysregulation of hepatic lipid homeostasis in common carp (Cyprinus carpio)

TBBPA, a ubiquitously distributed brominated flame retardant, poses significant ecological risks due to its bioaccumulative potential and toxicity. Previous investigations have predominantly focused on untargeted metabolomics and lipidomics to characterize the effects of TBBPA on metabolic end products. However, limited data are available regarding the mechanisms underlying TBBPA-induced disruption of lipid metabolism in aquatic organisms. This study systematically investigated the dose-dependent effects of TBBPA on lipid metabolism in common carp through integrated biochemical, histochemical evaluations, and transcriptomic profiling. Fish were exposed to environmentally relevant TBBPA concentrations (0, 0.005, 0.05, and 0.5 mg/L) for a 14-day duration. Serum biochemical analyses revealed dose-dependent hyperlipidemia, manifested by elevated TG and T-CHO levels, suppressed SOD and CAT activities, and increased MDA levels. Oil Red O staining demonstrated hepatic lipid droplet accumulation despite no significant ( P  > 0.05) alterations in intrahepatic TG/T-CHO content, with the 0.5 mg/L group exhibited the most severe histopathological phenotype. Transcriptomic profiling identified the AMPK and PPAR signaling pathways as pivotal regulators of TBBPA-induced metabolic dysregulation. Under low-dose TBBPA exposure (0.05 mg/L), lipid accumulation triggered compensatory activation of the AMPK / PPAR-α / CPT1 axis, enhancing fatty acid β-oxidation to partially counteract lipid deposition. Conversely, high-dose TBBPA (0.5 mg/L) disrupted lipid metabolism through coordinated upregulation of genes associated with lipid synthesis, transport, and storage, culminating in pathological lipid deposition. This study provides critical insights into the molecular cascades underlying TBBPA-induced metabolic dysregulation in aquatic species, highlights the dose-dependent disruption of lipid homeostasis.