Teadenol A in microbial fermented tea acts as a novel ligand on GPR120 to increase GLP-1 secretion
Teadenol A in microbial fermented tea acts as a novel ligand on GPR120 to increase GLP-1 secretion
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微生物发酵茶中的 Teadenol A 作为 GPR120 的新型配体，可增加 GLP-1 的分泌
DOI：
10.1039/d0fo02442b
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发表时间：
2020
期刊：
影响因子：
6.1
通讯作者：
Susumu Mitsutake
中科院分区：
文献类型：
--
作者：
Tomotaka Nagasawa ;Kanji Ishimaru;Shigeki Higashiyama;Yoichiro Hama;Susumu Mitsutake
通过微生物发酵生产的后发酵茶由于其降低高脂血症和动脉粥样硬化风险的健康益处而引起关注。虽然已经从后发酵茶中鉴定出几种新的多酚，但它们的生物活性尚未完全阐明。在这项研究中，我们发现，茶烯醇A，最近从日本后发酵茶中分离出的多酚，作为一种新的配体的长链脂肪酸受体，GPR 120。Teadenol A激活的GPR 120在293 T细胞中过表达，并且这种激活被GPR 120拮抗剂AH 7614抑制。此外，茶腺醇A诱导293 T细胞Erk 1/2磷酸化，并增加细胞内Ca 2+浓度，这些作用完全依赖于GPR 120表达。我们的研究结果表明茶腺醇A直接结合并激活GPR 120。此外，茶腺醇A增强肠内分泌STC-1细胞分泌GLP-1。GLP-1抑制食欲并增加胰岛素分泌，表现出抗糖尿病作用。GPR 120/GLP-1信号作为治疗2型糖尿病药物的潜在靶点引起了人们的关注。我们的研究结果表明，茶烯醇A是后发酵茶中对代谢综合征有益的关键分子。
Post-fermented teas, produced by microbial fermentation, are attracting attention due to their health benefits that reduce the risk of hyperlipidemia and atherosclerosis. Although several novel polyphenols have been identified from post-fermented teas, their biological activities have not yet been fully elucidated. In this study, we found that teadenol A, a polyphenol recently isolated from Japanese post-fermented tea, acts as a novel ligand on a long-chain fatty acid receptor, GPR120. Teadenol A activated GPR120 was over-expressed in 293T cells, and this activation was inhibited by the GPR120 antagonist AH7614. Additionally, teadenol A induced Erk1/2 phosphorylation and increased the intracellular Ca2+ concentration in 293T cells, and these effects were completely dependent on GPR120 expression. Our results suggest that teadenol A binds and activates GPR120 directly. Furthermore, teadenol A enhanced the secretion of GLP-1 from intestinal endocrine STC-1 cells. GLP-1 suppresses appetite and increases insulin secretion, exhibiting anti-diabetic effects. GPR120/GLP-1 signaling is attracting attention as a potential target for pharmaceuticals against type 2 diabetes. Our results suggest that teadenol A is a key molecule in post-fermented tea responsible for beneficial effects on metabolic syndrome.