Omega-3 polyunsaturated fatty acids and the eicosapentaenoic acid metabolite 18-hydroxyeicosapentaenoic acid

Hiromu Miyake1, Kathryn E Hopperton2, Pekka Määttänen3

  • 1Division of General and Thoracic Surgery & Research Institute, Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G1X8, Canada; Department of Pediatric Surgery, Shizuoka Children's Hospital, 860 Urushiyama, Aoi-ku, Shizuoka 4208660, Japan.

Insights

Maternal omega-3 fatty acid intake protects premature infants from necrotizing enterocolitis (NEC). A specific metabolite, 18-HEPE, shows promise as a novel therapy for this serious neonatal intestinal disease.

Area of Science:

  • Neonatal research
  • Gastroenterology
  • Immunology

Background:

  • Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease affecting premature infants, often associated with intestinal inflammation.
  • Maternal intake of omega-3 polyunsaturated fatty acids (PUFAs) may offer protection against inflammatory conditions in newborns.

Purpose of the Study:

  • To investigate the protective effects of omega-3 fatty acids against intestinal injury in an experimental model of NEC.
  • To explore the potential role of omega-3 metabolites in preventing NEC.

Main Methods:

  • Mice dams were fed diets enriched with omega-3 fatty acids (fish oil) or omega-6 fatty acids (safflower oil).
  • Transgenic fat-1 mice, capable of endogenous omega-3 production, were used to model elevated omega-3 levels.
  • Intestinal injury, pro-inflammatory cytokine levels (IL-6, TNFα), and omega-3 metabolite levels (18-HEPE) were assessed in pups.

Main Results:

  • Pups born to dams fed fish oil exhibited significantly reduced mucosal injury scores and lower levels of pro-inflammatory cytokines compared to those fed safflower oil.
  • Similar protective effects were observed in fat-1 transgenic pups, indicating the benefit of increased omega-3 levels.
  • Elevated levels of 18-hydroxyeicosapentaenoic acid (18-HEPE) were found in the ilea of protected pups.
  • Exogenous administration of 18-HEPE also protected wild-type pups against intestinal injury.

Conclusions:

  • Maternal omega-3 supplementation effectively prevents intestinal injury in a mouse model of NEC.
  • The omega-3 metabolite 18-HEPE may mediate the protective effects against NEC.
  • 18-HEPE presents a potential therapeutic candidate for the prevention or treatment of neonatal intestinal injury.