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A gut microbial metabolite of linoleic acid and gut homeostasis
Author(s) -
Miyamoto Junki,
Kishino Shigenobu,
Suzuki Takuya,
Ogawa Jun,
Kimura Ikuo,
Tanabe Soichi
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.968.10
Subject(s) - linoleic acid , polyunsaturated fatty acid , chemistry , biochemistry , metabolite , gut flora , conjugated linoleic acid , metabolism , proinflammatory cytokine , tumor necrosis factor alpha , fatty acid , biology , inflammation , endocrinology , immunology
Gut microbial metabolites of polyunsaturated fatty acids have attracted much attention because of their various physiological properties (1) ( Fig). Dysfunction of TJ in the intestine contributes to the pathogenesis of many disorders such as IBD. We evaluated the effects of gut microbial metabolites on tumor necrosis factor TNF‐α‐induced barrier impairment in Caco‐2 cells and DSS‐induced colitis in mice. 10‐Hydroxy‐ cis ‐12‐octadecenoic acid (HYA), a gut microbial metabolite of linoleic acid, suppressed TNF‐α and DSS‐induced changes in the expression of TJ‐related molecules, occludin, zonula occludens‐1, and myosin light chain kinase. HYA also suppressed the expression of TNFR2 mRNA and protein expression in Caco‐2 cells and colonic tissue. In addition, HYA suppressed the protein expression of TNFR2 in murine intestinal epithelial cells. Furthermore, it was clearly shown that GPR40 recognizes HYA with higher affinity than linoleic acid, an endogenous agonist, and that the blockade of GPR40 signaling and MEK‐ERK pathway cancels the suppressive effects of HYA on intestinal inflammation. Conversely, 10‐hydroxyoctadacanoic acid (HYB), which is a gut microbial metabolite of oleic acid and lacks a carbon‐carbon double bond at Δ12 position, did not show these TJ‐restoring activities. Therefore, HYA modulates TNFR2 expression, at least partially, via the GPR40‐MEK‐ERK pathway and may be useful in the treatment of TJ‐related disorders such as IBD (2) . FigPolyunsaturated fatty acid‐metabolism pathway (1)