Transcriptional Response to Palmitic Acid-Induced Lipid Droplet Accumulation in Primary Adherent Mantle Cells of Sinonovacula constricta (Lamarck 1818)

Palmitic acid (PA) is the most abundant saturated fatty acid in the diet of marine bivalves, yet its cellular regulatory mechanisms remain unclear. Using primary adherent mantle cells from the razor clam Sinonovacula constricta, we examined PA-induced lipid droplet (LD) accumulation and the underlying transcriptomic responses. We established that L-15 medium supplemented with 10% FBS provided optimal culture conditions. Oil Red O staining demonstrated that PA triggered a dose-dependent increase in LD content, with significant deposition evident at 50 μM. Transcriptomic profiling revealed 885 differentially expressed genes (477 up- and 408 downregulated), primarily enriched for lipid metabolism (e.g., PPAR and glycerophospholipid pathways), ER stress responses (e.g., protein processing and autophagy), and cytoskeletal organization. PA treatment was associated with upregulation of PLIN2, SCD, and HMGCS1 and downregulation of the fatty acid oxidation gene FABP3, suggesting a transcriptional shift toward lipid storage and reduced fatty acid oxidation. Concomitantly, PA may activate the ER stress response, as suggested by the dramatic induction of HSPA5, EIF2AK3, and DNAJC3. Our findings provide cellular evidence in bivalves that PA is associated with LD accumulation, potentially through integrated transcriptional changes in lipid metabolic and ER stress pathways, offering a reference for nutritional regulation strategies in S. constricta aquaculture. However, the causal relationships between these transcriptional changes and functional outcomes require further validation through protein-level and in vivo studies.