@article{570b820f3b464162bd8a1f3c6af58bdc,
title = "Dietary ω3 fatty acid exerts anti-allergic effect through the conversion to 17,18-epoxyeicosatetraenoic acid in the gut",
abstract = "ω3 polyunsaturated fatty acids (PUFAs) have anti-allergic and anti-inflammatory properties, but the immune-metabolic progression from dietary oil remains to be investigated. Here we identified 17,18-epoxyeicostetraenoic acid (17,18-EpETE) as an anti-allergic metabolite generated in the gut from dietary ω3 α-linolenic acid (ALA). Biochemical and imaging mass spectrometry analyses revealed increased ALA and its metabolites, especially eicosapentaenoic acid (EPA), in the intestines of mice receiving ALA-rich linseed oil (Lin-mice). In murine food allergy model, the decreased incidence of allergic diarrhea in Lin-mice was due to impairment of mast cell degranulation without affecting allergen-specific serum IgE. Liquid chromatography-tandem mass spectrometry-based mediator lipidomics identified 17,18-EpETE as a major ω3 EPA-derived metabolite generated from dietary ALA in the gut, and 17,18-EpETE exhibits anti-allergic function when administered in vivo. These findings suggest that metabolizing dietary ω3 PUFAs generates 17,18-EpETE, which is an endogenous anti-allergic metabolite and potentially is a therapeutic target to control intestinal allergies.",
author = "Jun Kunisawa and Makoto Arita and Takahiro Hayasaka and Takashi Harada and Ryo Iwamoto and Risa Nagasawa and Shiori Shikata and Takahiro Nagatake and Hidehiko Suzuki and Eri Hashimoto and Yosuke Kurashima and Yuji Suzuki and Hiroyuki Arai and Mitsutoshi Setou and Hiroshi Kiyono",
note = "Funding Information: This work was supported by grants from the Science and Technology Research Promotion Program for Agriculture, Forestry, Fisheries and Food Industry (J.K.); the Program for Promotion of Basic and Applied Research for Innovations in Bio-oriented Industry (J.K.); Japan Science and Technology Agency Precursory Research for Embryonic Science and Technology (PRESTO) (M.A.); the Ministry of Education, Culture, Sports, Science and Technology of Japan (Grants-in-Aid for Scientific Research on Innovative Areas [J.K., M.A., M.S.]; for Challenging Exploratory Research [J.K.], for Scientific Research B [J.K., M.S.]; Project for Creation of Research Platforms and Sharing of Advanced Research Infrastructure [M.S.]; for Scientific Research S [H.K.]; Translational Research Network Program [J.K.]; and for the Leading-edge Research Infrastructure Program [J.K. and H.K.]); and from the Ministry of Health and Welfare of Japan (J.K. and H.K.), Ono Medical Research Foundation (J.K.); Kishimoto Foundation Research Grant (J.K.); and the Naito Foundation (J.K.).",
year = "2015",
month = jun,
day = "11",
doi = "10.1038/srep09750",
language = "English",
volume = "5",
journal = "Scientific reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
}