(-)-Catechin promotes adipocyte differentiation in human bone marrow mesenchymal stem cells through PPARγ transactivation

(-)-Catechin promotes adipocyte differentiation in human bone marrow mesenchymal stem cells through PPARγ transactivation
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DOI:
10.1016/j.bcp.2008.09.033
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发表时间:
2009-01-01
影响因子:
5.8
通讯作者:
Noh, Minsoo
Noh, Minsoo
中科院分区:
医学2区
文献类型:
--
作者:
Shin, Dong Wook;Kim, Su Nam;Noh, Minsoo

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绿色茶的摄入已被证明可以为患有代谢紊乱的患者带来各种健康益处。在这里,我们研究了几种主要的绿色茶多酚对人骨髓间充质干细胞(hBM-MSCs)脂肪细胞分化的影响,并将其与代表性的抗糖尿病药物的效果进行比较。(-)-儿茶素是评价的八种绿色茶多酚中促进hBM-MSCs脂肪细胞分化的最有效的,并且这种作用是剂量依赖性的。(-)-儿茶素增加了各种脂肪形成标志物的mRNA水平,如脂联素、过氧化物酶体增殖物激活受体γ(过氧化物酶体增殖物激活受体γ)、FABP 4和LPL,如在hBM-MSC中脂肪细胞分化期间所测量的。此外,(-)-儿茶素上调hBM-MSC培养中脂联素的分泌。使用报告基因测定和竞争性配体结合研究,儿茶素也以剂量依赖性方式显著激活PPAR γ;然而,儿茶素,(-)-儿茶素的对映体,作为PPAR γ激动剂是无效的,这似乎暗示(-)-儿茶素对PPAR γ的作用是立体特异性的。总之,我们的数据表明,(-)-儿茶素促进脂肪细胞分化和增加对胰岛素的敏感性部分是通过直接激活过氧化物酶体增殖物激活受体γ,这可能是观察到的绿色茶摄入在降低2型糖尿病风险方面的药理学益处的基础。(C)2008年爱思唯尔公司All rights reserved.
Green tea intake has been shown to confer various health benefits to patients suffering from metabolic disorders. Here, we studied the effect of several major green tea polyphenols on adipocyte differentiation in human bone marrow mesenchymal stem cells (hBM-MSCs) and compared it to the effect of representative antidiabetic drugs. (-)-Catechin was the most potent of the eight green tea polyphenols evaluated in promoting adipocyte differentiation in hBM-MSCs, and this effect was dose-dependent. (-)-Catechin increased the mRNA levels of various adipogenic markers, such as adiponectin, peroxisome proliferator-activated receptor gamma (PPAR gamma), FABP4, and LPL, as measured during adipocyte differentiation in hBM-MSCs. In addition, (-)-catechin upregulated the secretion of adiponectin in hBM-MSC culture. Using a reporter gene assay and a competitive ligand binding study, catechin also significantly activated PPAR gamma in a dose-dependent fashion; however, catechin, the enantiomer of (-)-catechin, was not effective as a PPAR gamma agonist, which seems to imply that the effect of (-)-catechin on PPAR gamma is stereospecific. in conclusion, our data suggest that (-)-catechin promotes adipocyte differentiation and increased sensitivity to insulin in part by direct activation of PPAR gamma, which could be at the basis of the observed pharmacological benefits of green tea intake in reducing the risk of type 2 diabetes. (C) 2008 Elsevier Inc. All rights reserved.