Wnt/Lrp/β-catenin signaling suppresses adipogenesis by inhibiting mutual activation of PPARγ and C/EBPα
Wnt/Lrp/β-catenin signaling suppresses adipogenesis by inhibiting mutual activation of PPARγ and C/EBPα
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DOI：
10.1016/j.bbrc.2007.08.088
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发表时间：
2007-11-16
影响因子：
3.1
通讯作者：
Ozono, Keiichi
中科院分区：
文献类型：
--
作者：
Kawai, Masanobu;Mushiake, Sotaro;Ozono, Keiichi
Wnt/β-连环蛋白信号传导与抑制脂肪生成有关。多项证据表明，可能的机制是阻断 PPAR γ 诱导。然而，确切的机制仍有待阐明。在这项研究中，我们证明 Wnt3a 条件培养基通过抑制 PPAR7 诱导来抑制 C/EBPP/δ 诱导的 3T3-L1 细胞脂肪生成。此外，Wnt3a 存在时，PPAR γ 和 C/EBP α 的相互激活也受到抑制。为了进一步研究经典 Wnt 通路在脂肪形成中的作用，我们使用从 Lrp6 缺陷胚胎中分离的小鼠胚胎成纤维细胞 (MEF)。与野生型MEF相反，Lrp6缺陷的MEF表现出自发的脂肪生成并逃脱了外源Wnt3a的抑制作用。这些发现表明 Wnt/Lrp6/β-catenin 信号在间充质干细胞的脂肪生成和细胞命运决定中发挥关键作用。 (C) 2007 Elsevier Inc. 保留所有权利。
Wnt/beta-catenin signaling has been implicated in repressing adipogenesis. Several lines of evidence show that the possible mechanism is blockade of PPAR gamma induction. However, the precise mechanisms remain to be elucidated. In this study, we demonstrated that Wnt3a conditioned medium suppresses C/EBPP/delta-induced adipogenesis of 3T3-L1 cells by inhibiting PPAR7 induction. In addition, the mutual activation of PPAR gamma and C/EBP alpha was also repressed in the presence of Wnt3a. To further investigate the role of the canonical Wnt pathway in adipogenesis, we used mouse embryonic fibroblasts (MEFs) isolated from Lrp6-deficient embryos. Contrary to wild-type MEFs, Lrp6-deficient MEFs showed spontaneous adipogenesis and escaped the suppressive effect of exogenous Wnt3a. These findings suggest a critical role of Wnt/Lrp6/beta-catenin signaling in adipogenesis and cell fate decision of mesenchymal stem cells. (C) 2007 Elsevier Inc. All rights reserved.