Regulatory Functions of Fatty Acid Synthase on Redox Homeostasis and Lipid-Immune Crosstalk in Primary Hepatocytes of Cyprinus carpio var. Jian: A Comprehensive Evaluation of Antioxidant Capacity, Fatty Acid Profiles and Transcriptomic Signaling

Fatty acid synthase (FASN) is the rate-limiting core enzyme for de novo fatty acid biosynthesis in aquatic animals, yet its regulatory role in teleost cellular antioxidant defense and redox balance remains poorly characterized. In this study, we identified and bioinformatically characterized the complete coding sequence (CDS) of Jian carp FASN, which encodes a 2514-amino acid polypeptide containing five conserved polyketide synthase (PKS) catalytic domains and 188 phosphorylation sites. qRT-PCR tissue profiling revealed ubiquitous FASN transcription across all tested tissues, with the highest abundance in liver tissue. To decipher the physiological functions of FASN, siRNA-mediated functional depletion was performed in isolated primary Jian carp hepatocytes. Suppression of endogenous FASN expression induced markers of oxidative damage, evidenced by significantly reduced activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) (p < 0.05), alongside elevated malondialdehyde (MDA) levels (p < 0.05). GC-MS detected global declines in cellular saturated, monounsaturated and polyunsaturated fatty acids, especially C14:0, C16:0 and C18:0. Transcriptionally, the 6-PGD was downregulated (p < 0.05), whereas the fatty acid oxidation gene PPARα was upregulated (p < 0.05). RNA-seq identified 13,546 differentially expressed genes, with enrichment analyses indicating transcriptional shifts associated with oxidative damage and NF-κB-related inflammatory signaling. A total of 23 hub genes related to lipid turnover and arachidonic acid metabolism were screened. Collectively, our results demonstrate that FASN acts as an essential upstream regulator of hepatic redox balance in Jian carp. FASN disrupts fatty acid pools and triggers metabolic–inflammatory reprogramming, offering new insights into lipid–antioxidant crosstalk in teleost hepatocytes.