Omega-3 fatty acids exacerbate DSS-induced colitis through decreased adiponectin in colonic subepithelial myofibroblasts

Inflamm Bowel Dis. 2008 Oct;14(10):1348-57. doi: 10.1002/ibd.20491.

Abstract

Background: Although the immunoregulatory effects of omega-3 fatty acid and adiponectin have been postulated, their role in intestinal inflammation is controversial. The aim of this study was to determine whether dietary fat intake influences activity of colonic inflammation through modulating this system.

Methods: C57BL/6 mice received dextran sulfate sodium for induction of colitis. Mice were fed a control diet, omega-3 fat-rich diet, omega-6 fat-rich diet, or saturated fat-rich diet. Some mice were administered a peroxisome proliferator activated receptor-gamma; agonist, pioglitazone. Messenger RNA expression of adiponectin and its receptors were analyzed. Adiponectin expression in colonic mucosa of ulcerative colitis patients was also analyzed.

Results: The receptors for adiponectin were found to be ubiquitously expressed in epithelial cells, intraepithelial lymphocytes, lamina proprial mononuclear cells, and subepithelial myofibroblasts from colonic tissue, but adiponectin was only expressed in myofibroblasts. Induction of colitis significantly decreased the expression of adiponectin in colonic mucosa. The omega-3 fat diet group, but not the other fat diet groups, showed exacerbated colitis with a further decrease of adiponectin expression. Pioglitazone treatment ameliorated the level of decrease in adiponectin expression and improved colonic inflammation induced by the omega-3 fat-rich diet. In patients with ulcerative colitis, the expression level of adiponectin in colonic mucosa was also decreased compared with that in control mucosa.

Conclusions: Adiponectin was found to be expressed in myofibroblasts. Adiponectin expression was significantly suppressed by induction of colitis, and aggravation of colitis after exposure to omega-3 fat may be due to a further decrease in the expression level of adiponectin.

MeSH terms

  • Adiponectin / genetics
  • Adiponectin / metabolism*
  • Animals
  • Anti-Inflammatory Agents / administration & dosage
  • Cells, Cultured
  • Colitis / chemically induced*
  • Colitis / drug therapy*
  • Colitis / metabolism
  • Colitis / pathology
  • Dextran Sulfate / toxicity
  • Dietary Fats / administration & dosage
  • Dietary Fats, Unsaturated / administration & dosage*
  • Disease Models, Animal
  • Fatty Acids, Omega-3 / administration & dosage*
  • Fatty Acids, Omega-6 / administration & dosage
  • Gene Expression
  • Humans
  • Intestinal Mucosa / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Myoblasts / metabolism*
  • Pioglitazone
  • RNA, Messenger / metabolism
  • Random Allocation
  • Reverse Transcriptase Polymerase Chain Reaction
  • Thiazolidinediones

Substances

  • Adiponectin
  • Anti-Inflammatory Agents
  • Dietary Fats
  • Dietary Fats, Unsaturated
  • Fatty Acids, Omega-3
  • Fatty Acids, Omega-6
  • RNA, Messenger
  • Thiazolidinediones
  • Dextran Sulfate
  • Pioglitazone