Flaxseed Oil Attenuates Intestinal Damage and Inflammation by Regulating Necroptosis and TLR4/NOD Signaling Pathways Following Lipopolysaccharide Challenge in a Piglet Model

Mol Nutr Food Res. 2018 May;62(9):e1700814. doi: 10.1002/mnfr.201700814. Epub 2018 Apr 14.

Abstract

Scope: Flaxseed oil is a rich source of α-linolenic acid (ALA), which is the precursor of the long-chain n-3 polyunsaturated fatty acids (PUFAs), including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). This study investigates the protective effect of flaxseed oil against intestinal injury induced by lipopolysaccharide (LPS).

Materials and results: Twenty-four weaned pigs were used in a 2 × 2 factorial experiment with dietary treatment (5% corn oil vs 5% flaxseed oil) and LPS challenge (saline vs LPS). On day 21 of the experiment, pigs were administrated with LPS or saline. At 2 h and 4 h post-administration, blood samples were collected. After the blood harvest at 4 h, all piglets were slaughtered and intestinal samples were collected. Flaxseed oil supplementation led to the enrichment of ALA, EPA, and total n-3 PUFAs in intestine. Flaxseed oil improved intestinal morphology, jejunal lactase activity, and claudin-1 protein expression. Flaxseed oil downregulated the mRNA expression of intestinal necroptotic signals. Flaxseed oil also downregulated the mRNA expression of intestinal toll-like receptors 4 (TLR4) and its downstream signals myeloid differentiation factor 88 (MyD88), nuclear factor kappa B (NF-κB), and nucleotide-binding oligomerization domain proteins 1, 2 (NOD1, NOD2) and its adapter molecule, receptor-interacting protein kinase 2 (RIPK2).

Conclusion: These results suggest that dietary addition of flaxseed oil enhances intestinal integrity and barrier function, which is involved in modulating necroptosis and TLR4/NOD signaling pathways.

Keywords: flaxseed oil; inflammation; intestinal barrier function; lipopolysaccharide; necroptosis signaling pathway; weaned pigs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis* / drug effects
  • Body Weight
  • Crosses, Genetic
  • Enterocolitis, Necrotizing / blood
  • Enterocolitis, Necrotizing / chemically induced
  • Enterocolitis, Necrotizing / metabolism
  • Enterocolitis, Necrotizing / prevention & control*
  • Gene Expression Regulation, Developmental / drug effects
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / growth & development
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / metabolism*
  • Intestines / drug effects
  • Intestines / growth & development
  • Intestines / immunology
  • Linseed Oil / adverse effects
  • Linseed Oil / therapeutic use*
  • Lipopolysaccharides / toxicity
  • Male
  • Nod1 Signaling Adaptor Protein / genetics
  • Nod1 Signaling Adaptor Protein / metabolism
  • Nod2 Signaling Adaptor Protein / genetics
  • Nod2 Signaling Adaptor Protein / metabolism
  • Orchiectomy / veterinary
  • Protective Agents / adverse effects
  • Protective Agents / therapeutic use
  • Random Allocation
  • Receptor-Interacting Protein Serine-Threonine Kinase 2 / genetics
  • Receptor-Interacting Protein Serine-Threonine Kinase 2 / metabolism
  • Signal Transduction*
  • Sus scrofa
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / metabolism*
  • Weaning
  • alpha-Linolenic Acid / adverse effects
  • alpha-Linolenic Acid / metabolism
  • alpha-Linolenic Acid / therapeutic use*

Substances

  • Lipopolysaccharides
  • Nod1 Signaling Adaptor Protein
  • Nod2 Signaling Adaptor Protein
  • Protective Agents
  • Toll-Like Receptor 4
  • lipopolysaccharide, E coli O55-B5
  • alpha-Linolenic Acid
  • Linseed Oil
  • Receptor-Interacting Protein Serine-Threonine Kinase 2