Hasan Arif U, Ohmori Koji, Konishi Kumi, Igarashi Junsuke, Hashimoto Takeshi, Kamitori Kazuyo, Yamaguchi Fuminori, Tsukamoto Ikuko, Uyama Toru, Ishihara Yasuhiro, Noma Takahisa, Tokuda Masaaki, Kohno Masakazu
Department of Cardiorenal and Cerebrovascular Medicine, Faculty of Medicine, Kagawa University, 1750-1, Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan.
Department of Cardiorenal and Cerebrovascular Medicine, Faculty of Medicine, Kagawa University, 1750-1, Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan.
Mol Cell Endocrinol. 2015 May 5;406:10-8. doi: 10.1016/j.mce.2015.02.012. Epub 2015 Feb 16.
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.
脂肪细胞释放的血管内皮生长因子A（VEGF-A）可促进血管生成，从而改善局部缺氧诱导的脂肪炎症和胰岛素抵抗。在此，我们首次发现二十碳五烯酸（EPA）上调成熟3T3-L1脂肪细胞中VEGF-A的mRNA表达和释放。沉默G蛋白偶联受体120（GPR120）的mRNA以及用GW9662特异性抑制过氧化物酶体增殖物激活受体γ（PPARγ），分别减弱了EPA诱导的脂肪细胞VEGF-A释放增加。此外，通过荧光素酶报告基因检测评估，单独将GPR120基因和单独将PPARγ基因转染至HEK293细胞，分别增加了VEGF-A的启动子活性，当两个基因共转染时，启动子活性进一步增强。启动子缺失分析和染色质免疫沉淀试验表明，GPR120的共转染增强了EPA诱导的PPARγ与VEGF-A启动子区域的PPAR反应元件的结合。因此，通过膜受体GRP120和核受体PPARγ的同步激活，EPA增强了脂肪细胞中VEGF-A的产生。
