Omega-6-associated gene modules reveal novel regulatory mechanisms in porcine liver

Identifying diets with desirable ratios of omega-6 (n-6) and omega-3 (n-3) fatty acids (FAs) plays a key role in regulating inflammation, maintaining membrane fluidity, facilitating β-oxidation, and promoting overall metabolic health. Previously, we showed that pigs fed 1.5% soybean oil (SOY1.5) had greater hepatic linoleic acid (an n-6 FA) deposition than pigs fed 3.0% soybean oil (SOY3.0). A balanced dietary ratio of n-6:n-3 FA is crucial to support optimal health and reduce the risk of chronic diseases. Thus, this study aimed to identify gene co-expression modules correlated with n-6 deposited in hepatic tissue of pigs fed diets containing either SOY 1.5 or SOY3.0. mRNA-seq data from 35 immunocastrated Large White pigs (CEUA2018-28) were analyzed using standard bioinformatics pipelines. Co-expression modules were identified with WGCNA, followed by functional enrichment using DAVID. Strong co-expression patterns related to n-6 were observed in both diets, but they involved distinct modules and pathways. In pigs fed SOY1.5, one gene cluster was negatively correlated with linoleic acid and total n-6. In pigs fed SOY3.0, however, another module was negatively correlated with the n-6:n-3 ratio. Functional enrichment analysis (FDR < 0.05) highlighted the fatty acid degradation pathway (ssc00071) in SOY1.5-fed pigs and Bile secretion pathway (ssc04976) in the SOY3.0 group. These findings suggest that dietary oil inclusion modulates distinct co-expression networks and metabolic pathways in porcine liver. These molecular insights can optimize nutritional strategies, thereby enhancing animal health and aligning with the FAO’s One Health initiative.