A gut microbial metabolite of linoleic acid, 10-hydroxy-cis-12-octadecenoic acid, ameliorates intestinal epithelial barrier impairment partially via GPR40-MEK-ERK pathway
Miyamoto J, Mizukure T, Park SB, Kishino S, Kimura I, Hirano K, Bergamo P, Rossi M, Suzuki T, Arita M, Ogawa J, Tanabe S
The Journal of biological chemistry · 200 citations
Review labels
Neutral facts our review recorded about how this study was done. They describe method, never whether we like the result.
How it was studied
- Design
- In vitro/mechanistic study (classified by our AI screen)
- Studied in
- People, plus animal or lab work
- Main outcome
- Mechanisms only
Who paid for it
- Funding
- Independent funding
- Government
- Japan Society for the Promotion of Science
- Government
- Bio-oriented Technology Research Advancement Institution
- Grants
- Japan Society for the Promotion of Science (22380076); Japan Society for the Promotion of Science (25292074); Japan Society for the Promotion of Science (14J06559)
Based on 2 listed funder(s).
Publication
- Published
- 2014-12-11 · J Biol Chem · vol. 290 · issue 5 · pp. 2902–2918
- Publisher
- Elsevier BV
- Cited
- 269 citations · more than 97% of similar papers · 5.4× the field average
- Impact
- Top 10% most cited in its field
- References
- 64 works
- Access
- Open access (hybrid journal) · CC-BY
- Research areas
- Gut microbiota and health · Helicobacter pylori-related gastroenterology studies · Barrier Structure and Function Studies
- Keywords
- Linoleic acid, Chemistry, Biochemistry, MAPK/ERK pathway, Metabolite, Tumor necrosis factor alpha, Conjugated linoleic acid, Biology, Signal transduction, Fatty acid, Endocrinology
- MeSH
- intestines, caco-2 cells, epithelial cells, animals, mice, inbred balb c, humans, mice, colitis, linoleic acid, oleic acids, receptors, g-protein-coupled, flow cytometry, immunohistochemistry, map kinase signaling system, female
12 authors
From JP, IT
- Junki MiyamotoHiroshima University
- Taichi MizukureHiroshima University
- Si-Bum ParkKyoto University
- Shigenobu KishinoKyoto University
- Ikuo KimuraKyoto University; Tokyo University of Agriculture and Technology
- Kanako HiranoKyoto University
Abstract
Gut microbial metabolites of polyunsaturated fatty acids have attracted much attention because of their various physiological properties. Dysfunction of tight junction (TJ) in the intestine contributes to the pathogenesis of many disorders such as inflammatory bowel disease. We evaluated the effects of five novel gut microbial metabolites on tumor necrosis factor (TNF)-α-induced barrier impairment in Caco-2 cells and dextran sulfate sodium-induced colitis in mice. 10-Hydroxy-cis-12-octadecenoic acid (HYA), a gut microbial metabolite of linoleic acid, suppressed TNF-α and dextran sulfate sodium-induced changes in the expression of TJ-related molecules, occludin, zonula occludens-1, and myosin light chain kinase. HYA also suppressed the expression of TNF receptor 2 (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, HYA significantly up-regulated G protein-coupled receptor (GPR) 40 expression in Caco-2 cells. It also induced [Ca(2+)]i responses in HEK293 cells expressing human GPR40 with higher sensitivity than linoleic acid, its metabolic precursor. The barrier-recovering effects of HYA were abrogated by a GPR40 antagonist and MEK inhibitor in Caco-2 cells. Conversely, 10-hydroxyoctadacanoic acid, 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 and down-regulated GPR40 expression. 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 inflammatory bowel disease.
Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY).
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