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.

Group X Secreted Phospholipase A2 Releases ω3 Polyunsaturated Fatty Acids, Suppresses Colitis, and Promotes Sperm Fertility

“…Although our study failed to show the ameliorating effect of resolvins and 18-HEPE on Th17 cytokine production by these cells, it is possible that these pro-resolving mediators could affect other steps of colitis, for instance by acting directly on epithelial cells to protect from injuries and on neutrophils to suppress their migration and to promote their clearance. In fact, resolvins block colitis when administered exogenously (47)(48)(49), and an endogenous EPA-derived epoxide attenuates allergic colitis (65).…”

EPA and/or DHA? A test question on the principles and opportunities in utilizing the therapeutic potential of omega-3 fatty acids

“…The EPA-derived 17,18-EEQ and its sEH-generated diol (17,18-DiHETE) became the predominant metabolites, surprisingly, not only after giving the ERO but also the DRO test meal. In contrast, the metabolism of DHA via the same CYP epoxygenase/ sEH-pathway was detectable only by an increase of the diol metabolite (19, that occurred specifically in the DRO group. Taking the sum of epoxy and diol metabolites, the EPA-derived metabolites exceeded the ones from DHA by a factor of 15 postprandial to the EPA-rich meal and still 8-fold after the DHA-rich meal.…”

“…17,18-EEQ appears to function as a highly potent mediator of cardioprotective and antiarrhythmic effects of EPA (13). As demonstrated in in vitro and animal studies, 17,18-EEQ also displays vasodilatory, anti-inflammatory, and anti-allergic properties that contribute to the beneficial effects of n-3 LC-PUFAs in diverse disease states ranging from bronchial disorders (16), fatty liver disease (17), and intraocular neovascularization (18) to allergic intestinal inflammation (19). The DHA-derived 19,20-epoxydocosapentaenoic acid (19,20-EDP alias 19,20-Ep-DPE) shares several of these properties but has attracted the most attention due to its capacity to inhibit tumor angiogenesis and proliferation (20).…”

ω3-Polyunsaturated fatty acids for heart failure: Effects of dose on efficacy and novel signaling through free fatty acid receptor 4

“…This is illustrated by the benefit observed with inhibitors of soluble epoxide hydrolase inhibitors, the enzyme that metabolizes PUFA epoxides, which include induction of angiogenesis [86, 87], and broad anti-inflammatory actions, including promotion of M2 macrophage polarization in the heart [88], which would all benefit HF. Furthermore, EPA-epoxides are reportedly up to 100 times more potent than those made from arachadonic acid [89], and the EPA epoxide, 17,18-epoxy eicosatetraenoic acid, suppresses both pulmonary [90] and gut inflammation [91]. …”