RRC ID 32799
Author Hasan AU, Ohmori K, Konishi K, Igarashi J, Hashimoto T, Kamitori K, Yamaguchi F, Tsukamoto I, Uyama T, Ishihara Y, Noma T, Tokuda M, Kohno M.
Title Eicosapentaenoic acid upregulates VEGF-A through both GPR120 and PPARγ mediated pathways in 3T3-L1 adipocytes.
Journal Mol. Cell. Endocrinol.
Abstract Vascular endothelial growth factor-A (VEGF-A) released from adipocytes promotes angiogenesis; and thereby ameliorates the local hypoxia-induced adipose inflammation and insulin resistance. Here, we newly found that eicosapentaenoic acid (EPA) upregulated both mRNA expression and release of VEGF-A in mature 3T3-L1 adipocytes. Silencing mRNA of G-protein coupled receptor 120 (GPR120) and specific inhibition of peroxisome proliferator-activated receptor γ (PPARγ) by GW9662 respectively attenuated the EPA-induced augmentation of VEGF-A release by adipocytes. Furthermore, transfection of GPR120 gene alone and PPARγ gene alone to HEK293 cells respectively increased the promoter activity of VEGF-A as assessed by luciferase reporter assay, which was further augmented when both genes were co-transfected. Promoter deletion analysis and chromatin immunoprecipitation assay revealed that co-transfection of GPR120 enhanced EPA-induced PPARγ binding to PPAR-response element in VEGF-A promoter region. Thus, by the synchronized activation of a membrane receptor GRP120 and a nuclear receptor PPARγ, EPA enhances VEGF-A production in adipocytes.
Volume 406
Pages 10-8
Published 2015-5-5
DOI 10.1016/j.mce.2015.02.012
PII S0303-7207(15)00088-X
PMID 25697344
MeSH 3T3-L1 Cells Adipocytes / drug effects Adipocytes / metabolism* Animals Eicosapentaenoic Acid / pharmacology* HEK293 Cells Humans Hypoxia-Inducible Factor 1, alpha Subunit / metabolism Mice Models, Biological PPAR gamma / metabolism* Phosphatidylinositol 3-Kinases / metabolism Protein Binding / drug effects Protein Kinase C / metabolism Receptors, G-Protein-Coupled / metabolism* Response Elements / genetics Signal Transduction / drug effects* Up-Regulation / drug effects* Vascular Endothelial Growth Factor A / genetics* Vascular Endothelial Growth Factor A / metabolism
IF 3.693
Times Cited 19
DNA material pGL4-phVEGFA (RDB07681)