Fish oil attenuates liver injury caused by LPS in weaned pigs associated with inhibition of TLR4 and nucleotide-binding oligomerization domain protein signaling pathways.

This study evaluated whether fish oil exerted a hepatoprotective effect in a LPS-induced liver injury model via regulation of TLR4 and nucleotide-binding oligomerization domain protein (NOD) signaling pathways. 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). Fish oil resulted in enrichment of eicosapentaenoic acid, docosahexaenoic acid and total (n-3) polyunsaturated fatty acids in liver. Less severe liver injury was observed in pigs fed fish oil, as evidenced by improved serum biochemical parameters and less severe histological liver damage. In addition, higher expression of liver tight junction proteins, and lower hepatocyte proliferation and higher hepatocyte apoptosis were observed in pigs fed fish oil. The improved liver integrity in pigs fed fish oil was concurrent with reduced hepatic mRNA expression of TLR4, myeloid differentiation factor 88, IL-1 receptor-associated kinase 1 and TNF-α receptor-associated factor 6, and NOD1, NOD2 and receptor-interacting serine/threonine-protein kinase 2, as well as reduced hepatic protein expression of NF-κB p65, leading to reduced hepatic pro-inflammatory mediators. These results indicate that fish oil improves liver integrity partially via inhibition of TLR4 and NOD signaling pathways under an inflammatory condition.