A Gut Microbial Metabolite of Linoleic Acid, 10-Hydroxy-cis-12-octadecenoic Acid, Ameliorates Intestinal Epithelial Barrier Impairment Partially via GPR40-MEK-ERK Pathway

• DOI: 10.1074/jbc.m114.610733
• Publication Date: 2014-12-12T01:24:37Z
• Authors: Junki Miyamoto; Taichi Mizukure; Si-Bum Park; Shigenobu Kishino; Ikuo Kimura; Kanako Hirano; Paolo Bergamo; Mauro Rossi; Takuya Suzuki; Makoto Arita; Jun Ogawa; Soichi Tanabe
• Keywords: linoleic acid; colitis; MAP Kinase Signaling System; tight junction; metabolite; microbiome; tumor necrosis factor (TNF); Oleic Acids; Receptors, G-Protein-Coupled; Linoleic Acid; Mice; 03 medical and health sciences; Animals; Humans; G protein-coupled receptor; Mice, Inbred BALB C; 0303 health sciences; epithelial cell; Caco-2; Epithelial Cells; Colitis; Flow Cytometry; Immunohistochemistry; Intestines; Female; Caco-2 Cells

Gut microbial metabolites of polyunsaturated fatty acids have attracted much attention because their various physiological properties. Dysfunction tight junction (TJ) in the intestine contributes to pathogenesis many disorders such as inflammatory bowel disease. We evaluated effects five novel gut on tumor necrosis factor (TNF)-α-induced barrier impairment Caco-2 cells and dextran sulfate sodium-induced colitis mice. 10-Hydroxy-cis-12-octadecenoic acid (HYA), a metabolite linoleic acid, suppressed TNF-α changes expression TJ-related molecules, occludin, zonula occludens-1, myosin light chain kinase. HYA also TNF receptor 2 (TNFR2) mRNA protein colonic tissue. In addition, TNFR2 murine intestinal epithelial cells. Furthermore, significantly up-regulated G protein-coupled (GPR) 40 It induced [Ca2+]i responses HEK293 expressing human GPR40 with higher sensitivity than its metabolic precursor. The barrier-recovering were abrogated by antagonist MEK inhibitor Conversely, 10-hydroxyoctadacanoic which is oleic lacks carbon-carbon double bond at Δ12 position, did not show these TJ-restoring activities down-regulated expression. Therefore, modulates expression, least partially, via GPR40-MEK-ERK pathway may be useful treatment disease.Background: activity has recently attention.Results: A 10-hydroxy-cis-12-octadecenoic ameliorates impairments regulating pathway.Conclusion: HYA-induced signaling homeostasis.Significance: Our findings indicate function inflamed intestine. Background: attention. Results: pathway. Conclusion: homeostasis. Significance: