Dietary fish oil supplementation alters liver gene expressions to protect against LPS-induced liver injury in weanling piglets

Here, the potential mechanisms of the protective effects of fish oil against LPS-induced liver injury in a piglet model were investigated by using RNA sequencing. Twenty-four piglets were used in a 2 × 2 factorial design, and the main factors included diet (5% corn oil or 5% fish oil) and immunological challenge (LPS or saline, on d 19). All piglets were slaughtered at 4 h after challenge, and liver samples were collected. Fish oil improved liver morphology and reduced TNF-α, IL-1β and IL-6 productions after LPS challenge. RNA sequencing analysis showed fish oil had significant effect on the expressions of genes involved in immune response during LPS-induced inflammation. Selected gene expression changes were validated using quantitative RT-PCR. Fish oil reduced the expressions of pro-inflammatory genes IL1R1, IL1RAP, CEBPB and CRP, and increased that of anti-inflammatory genes IL-18BP, NFKBIA, IFIT1, IFIT2 and ATF3. Moreover, fish oil restored the expressions of some lipid metabolism-related genes, such as ACAA1, ACACA, ACADS and ACADM, which were only decreased in pigs fed a corn oil diet after LPS challenge. Our RNA sequencing reveals novel gene-nutrient interactions following fish oil supplementation and evoked inflammation, which add to the current understanding of the benefits of n-3 polyunsaturated fatty acids against liver injury.