Mechanisms of lipid metabolic disorder and inflammation in the clam Ruditapes philippinarum under PAHs stress

The mechanisms by which Polycyclic Aromatic Hydrocarbons (PAHs) induce lipid metabolic disorder and inflammation in marine invertebrates remain poorly understood. This study utilized the clam Ruditapes philippinarum during its reproductive stage as a model organism, integrating high-throughput omics, computational simulation, and confocal microscopy to elucidate the accumulation characteristics and toxicological pathways of PAHs. The results demonstrated that PAHs significantly accumulated in the digestive gland and gonads, primarily sequestered within lipid droplets. This tissue distribution was found to be dependent on a lipid-dependent transport mechanism mediated by ApoB, FATP, and FABP4. Mechanistically, PAHs activated SREBP1 and PPARα, β nuclear receptors by interfering with the neuroendocrine system and endoplasmic reticulum stress pathways. This activation resulted in dysregulated lipid metabolism (favoring synthesis over degradation) and subsequent abnormal lipid (TG, PL) deposition. Furthermore, PAHs induced low-grade inflammation by synergistically activating the NF-κB and AP-1 pathways, a response driven by both lipotoxicity and cellular organelle stress. This finding provides important scientific evidence for contaminant risk assessment in aquatic organisms. • PAHs accumulation correlates with TG and PL, predominantly stored in lipid droplets. • PAHs transport relied on ApoB across tissues and on FATP/FABP4 across cells. • PAHs activated SREBP1/PPARα,β via neuroendocrine/ER stress to modulate FA metabolism. • PAHs disrupted lipid metabolism, causing lipid accumulation, stronger in females. • PAHs triggered NF-κB/AP-1 via lipotoxic and oxidative stress to drive low-grade inflammation.