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Published on: February 27, 2014
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.
Abstract:
Necrotizing enterocolitis (NEC), a devastating gastrointestinal disease in infants born prematurely, is linked to intestinal inflammation. Maternal intake of omega-3 polyunsaturated fatty acids (PUFAs) has been reported as protective against inflammatory reactions in their offspring. We hypothesized that omega-3 fatty acids would prevent intestinal injury in an experimental model of NEC. Elevated omega-3 levels in mouse pups were achieved either by enriching dam-fed diets with omega-3 or by endogenous production in transgenic fat-1 mice able to convert omega-6 to omega-3. Mucosal injury scores decreased in pups of dams fed fish oil, compared to those fed safflower oil. Pro-inflammatory cytokines IL6 and TNFα were lower in pups of mothers fed fish oil, compared to those fed safflower oil. Comparable results were obtained in fat-1 transgenic pups. Elevated levels of 18-hydroxyeicosapentaenoic acid (18-HEPE) were detected in the distal ilea of pups in both models, suggesting that this eicosapentaenoic acid metabolite could mediate the observed protection. In the absence of maternal omega-3 supplementation, exogenous administration of 18-HEPE in wild-type pups, protected against intestinal injury. Maternal omega-3 supplementation prevented NEC and 18-HEPE could serve as a candidate novel therapy for either the prevention or treatment of neonatal intestinal injury.
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