Dietary ω3 fatty acid exerts anti-allergic effect through the conversion to 17,18-epoxyeicosatetraenoic acid in the gut

Jun Kunisawa, Makoto Arita, Takahiro Hayasaka, Takashi Harada, Ryo Iwamoto, Risa Nagasawa, Shiori Shikata, Takahiro Nagatake, Hidehiko Suzuki, Eri Hashimoto, Yosuke Kurashima, Yuji Suzuki, Hiroyuki Arai, Mitsutoshi Setou, Hiroshi Kiyono

Research output: Contribution to journalArticle

47 Citations (Scopus)

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.

Original languageEnglish
Article number9750
JournalScientific Reports
Volume5
DOIs
Publication statusPublished - 2015 Jun 11
Externally publishedYes

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Anti-Allergic Agents
Fatty Acids
Acids
Eicosapentaenoic Acid
Unsaturated Fatty Acids
Linseed Oil
Unsaturated Dietary Fats
Cell Degranulation
alpha-Linolenic Acid
Food Hypersensitivity
Tandem Mass Spectrometry
Mast Cells
Liquid Chromatography
Allergens
Immunoglobulin E
Intestines
Diarrhea
Mass Spectrometry
Hypersensitivity
Anti-Inflammatory Agents

ASJC Scopus subject areas

  • General

Cite this

Dietary ω3 fatty acid exerts anti-allergic effect through the conversion to 17,18-epoxyeicosatetraenoic acid in the gut. / Kunisawa, Jun; Arita, Makoto; Hayasaka, Takahiro; Harada, Takashi; Iwamoto, Ryo; Nagasawa, Risa; Shikata, Shiori; Nagatake, Takahiro; Suzuki, Hidehiko; Hashimoto, Eri; Kurashima, Yosuke; Suzuki, Yuji; Arai, Hiroyuki; Setou, Mitsutoshi; Kiyono, Hiroshi.

In: Scientific Reports, Vol. 5, 9750, 11.06.2015.

Research output: Contribution to journalArticle

Kunisawa, J, Arita, M, Hayasaka, T, Harada, T, Iwamoto, R, Nagasawa, R, Shikata, S, Nagatake, T, Suzuki, H, Hashimoto, E, Kurashima, Y, Suzuki, Y, Arai, H, Setou, M & Kiyono, H 2015, 'Dietary ω3 fatty acid exerts anti-allergic effect through the conversion to 17,18-epoxyeicosatetraenoic acid in the gut', Scientific Reports, vol. 5, 9750. https://doi.org/10.1038/srep09750
Kunisawa, Jun ; Arita, Makoto ; Hayasaka, Takahiro ; Harada, Takashi ; Iwamoto, Ryo ; Nagasawa, Risa ; Shikata, Shiori ; Nagatake, Takahiro ; Suzuki, Hidehiko ; Hashimoto, Eri ; Kurashima, Yosuke ; Suzuki, Yuji ; Arai, Hiroyuki ; Setou, Mitsutoshi ; Kiyono, Hiroshi. / Dietary ω3 fatty acid exerts anti-allergic effect through the conversion to 17,18-epoxyeicosatetraenoic acid in the gut. In: Scientific Reports. 2015 ; Vol. 5.
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