Fish oil enhances intestinal barrier function and inhibits corticotropin-releasing hormone/corticotropin-releasing hormone receptor 1 signalling pathway in weaned pigs after lipopolysaccharide challenge

Br J Nutr. 2016 Jun;115(11):1947-57. doi: 10.1017/S0007114516001100. Epub 2016 Apr 15.

Abstract

Stress induces injury in intestinal barrier function in piglets. Long-chain n-3 PUFA have been shown to exhibit potential immunomodulatory and barrier protective effects in animal models and clinical trials. In addition, corticotropin-releasing hormone (CRH)/CRH receptor (CRHR) signalling pathways play an important role in stress-induced alterations of intestinal barrier function. We hypothesised that fish oil could affect intestinal barrier function and CRH/CRHR signalling pathways. In total, thirty-two weaned pigs were allocated to one of four treatments. The experiment consisted of a 2×2 factorial design, and the main factors included immunological challenge (saline or lipopolysaccharide (LPS)) and diet (5 % maize oil or 5 % fish oil). On d 19 of the trial, piglets were treated with saline or LPS. At 4 h after injection, all pigs were killed, and the mesenteric lymph nodes (MLN), liver, spleen and intestinal samples were collected. Fish oil decreased bacterial translocation incidence and the number of translocated micro-organisms in the MLN. Fish oil increased intestinal claudin-1 protein relative concentration and villus height, as well as improved the intestinal morphology. In addition, fish oil supplementation increased intestinal intraepithelial lymphocyte number and prevented elevations in intestinal mast cell and neutrophil numbers induced by LPS challenge. Moreover, fish oil tended to decrease the mRNA expression of intestinal CRHR1, CRH and glucocorticoid receptors. These results suggest that fish oil supplementation improves intestinal barrier function and inhibits CRH/CRHR1 signalling pathway and mast cell tissue density.

Keywords: CRH corticotropin-releasing hormone; CRHR1 corticotropin-releasing hormone receptor 1; Fish oil; GR glucocorticoid receptor; HPA hypothalamo–pituitary–adrenall; IAP intestinal alkaline phosphatase; IEL intraepithelial lymphocytes; Intestinal barrier function; LPS lipopolysaccharide; Lipopolysaccharides; MLN mesenteric lymph nodes; Weaned pigs.

MeSH terms

  • Animals
  • Bacterial Translocation
  • Claudin-1 / metabolism
  • Corticotropin-Releasing Hormone / metabolism*
  • Dietary Fats, Unsaturated / pharmacology
  • Dietary Supplements
  • Fish Oils / pharmacology*
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology
  • Intestine, Small / drug effects*
  • Intestine, Small / metabolism
  • Intestine, Small / pathology
  • Lipopolysaccharides / adverse effects*
  • Male
  • Mast Cells / metabolism*
  • Neutrophils / metabolism
  • RNA, Messenger / metabolism
  • Receptors, Corticotropin-Releasing Hormone / genetics
  • Receptors, Corticotropin-Releasing Hormone / metabolism*
  • Receptors, Glucocorticoid / genetics
  • Receptors, Glucocorticoid / metabolism
  • Signal Transduction
  • Swine
  • Weaning

Substances

  • Claudin-1
  • Dietary Fats, Unsaturated
  • Fish Oils
  • Lipopolysaccharides
  • RNA, Messenger
  • Receptors, Corticotropin-Releasing Hormone
  • Receptors, Glucocorticoid
  • CRF receptor type 1
  • Corticotropin-Releasing Hormone