Zhang Yongchun, O'Keefe Regis J, Jonason Jennifer H
Center for Musculoskeletal Research, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, New York 14642.
Department of Biochemistry and Biophysics, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, New York 14642.
J Cell Biochem. 2017 Jan;118(1):204-210. doi: 10.1002/jcb.25626. Epub 2016 Jun 27.
BMPs have been shown to promote adipocyte differentiation through SMAD-dependent signaling. However, the role of TGF-β-activated kinase 1 (TAK1) in non-canonical BMP signaling in adipocyte differentiation remains unclear. Here, we show that TAK1 inhibition decreases lipid accumulation in C3H10T1/2 mesenchymal stem cells (MSCs) induced to differentiate into adipocytes. TAK1 knockdown by siRNA further confirms that TAK1 is required for adipocyte commitment of MSCs. Additionally, TAK1 knockdown inhibits adipogenesis of 3T3-L1 preadipocytes, indicating that TAK1 is not only needed for adipocyte commitment, but also required for adipocyte terminal differentiation. Furthermore, TAK1 ablation specifically in adipocytes reduced high fat diet-induced weight gain and improved glucose tolerance. Mechanistically, we demonstrate that TAK1 is required for PPARγ transactivation and promotes PPARγ transcriptional activity synergistically with TAK1 binding protein 1 (TAB1). Collectively, our results demonstrate that TAK1 plays a critical role in BMP-mediated adipocyte differentiation. J. Cell. Biochem. 118: 204-210, 2017. © 2016 Wiley Periodicals, Inc.
骨形态发生蛋白（BMPs）已被证明可通过SMAD依赖的信号传导促进脂肪细胞分化。然而，转化生长因子-β激活激酶1（TAK1）在脂肪细胞分化的非经典BMP信号传导中的作用仍不清楚。在此，我们表明TAK1抑制可减少诱导分化为脂肪细胞的C3H10T1/2间充质干细胞（MSCs）中的脂质积累。通过小干扰RNA（siRNA）敲低TAK1进一步证实TAK1是MSCs向脂肪细胞定向分化所必需的。此外，敲低TAK1可抑制3T3-L1前脂肪细胞的脂肪生成，表明TAK1不仅是脂肪细胞定向分化所必需的，也是脂肪细胞终末分化所必需的。此外，特异性敲除脂肪细胞中的TAK1可减少高脂饮食诱导的体重增加并改善葡萄糖耐量。从机制上讲，我们证明TAK1是过氧化物酶体增殖物激活受体γ（PPARγ）反式激活所必需的，并与TAK1结合蛋白1（TAB1）协同促进PPARγ转录活性。总体而言，我们的结果表明TAK1在BMP介导的脂肪细胞分化中起关键作用。《细胞生物化学杂志》118: 204 - 210, 2017。© 2016威利期刊公司
