Flaxseed oil improves liver injury and inhibits necroptotic and inflammatory signaling pathways following lipopolysaccharide challenge in a piglet model

The hepatoprotective effects of flaxseed oil (FO) were tested in a pig model of lipopolysaccharide (LPS)-induced liver injury. Twenty-four piglets were used in a 2 × 2 factorial design including diet and an LPS challenge. After 3 weeks of feeding with 5% FO or 5% corn oil, pigs were challenged with LPS or saline. FO alleviated LPS-induced morphological liver damage, reduced serum alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase activities, and increased claudin-1 protein expression. FO decreased tumor necrosis factor-α, interleukin-6 and cyclooxygenase 2 mRNA expression, and heat shock protein 70 mRNA and protein expression. FO downregulated receptor interacting protein kinase (RIP)1, RIP3, and mixed-lineage kinase domain-like protein (MLKL) mRNA expression, RIP1 and RIP3 protein expression, and MLKL phosphorylation. FO downregulated mRNA expression of toll-like receptor 4, nucleotide-binding oligomerization domain protein 1 and multiple downstream signaling molecules, and decreased p38 and extracellular signal-regulated kinase 1/2 phosphorylation. These results indicate that FO inhibits necroptotic and inflammatory signaling pathways to protect the liver from inflammation-related injury.