The roles of transforming growth factor-β and Smad3 signaling in adipocyte differentiation and obesity
The roles of transforming growth factor-β and Smad3 signaling in adipocyte differentiation and obesity
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DOI：
10.1016/j.bbrc.2011.02.106
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发表时间：
2011-04-01
影响因子：
3.1
通讯作者：
Yokote, Koutaro
中科院分区：
文献类型：
--
作者：
Tsurutani, Yuya;Fujimoto, Masaki;Yokote, Koutaro
我们的目的是阐明转化生长因子（TGF）-β和Smad 3信号在脂肪细胞分化（脂肪形成）和肥胖的发病机制中的作用。在遗传性肥胖（ob/ob）小鼠中测定白色脂肪组织（WAT）中的TGF-β/Smad 3信号传导。通过油红-O染色和基因表达分析，在从WT对照和Smad 3 KO小鼠分离的小鼠胚胎成纤维细胞（MEF）中评价TGF-β对脂肪形成的作用。与WT对照相比，在Smad 3 KO小鼠中进行高脂饮食（HFD）诱导的肥胖的表型分析。与对照组相比，ob/ob小鼠的WAT中TGF-β/Smad 3信号传导升高。TGF-β显著抑制MEF中的脂肪生成，但TGF-β对脂肪生成的抑制作用在Smad 3 KO小鼠的MEF中被部分消除。TGF-β独立于Wnt和β-连环蛋白途径抑制脂肪形成。保护Smad 3 KO小鼠免受HFD诱导的胰岛素抵抗。来自HFD的Smad 3 KO小鼠的脂肪细胞的大小与对照相比显著更小。总之，TGF-β/Smad 3信号通路不仅在脂肪形成中起关键作用，而且在胰岛素抵抗的发展中也起关键作用。(C)2011 Elsevier Inc. All rights reserved.
We aimed at elucidating the roles of transforming growth factor (TGF)-beta and Smad3 signaling in adipocyte differentiation (adipogenesis) and in the pathogenesis of obesity. TGF-beta/Smad3 signaling in white adipose tissue (WAT) was determined in genetically obese (ob/ob) mice. The effect of TGF-beta on adipogenesis was evaluated in mouse embryonic fibroblasts (MEF) isolated both from WT controls and Smad3 KO mice by Oil red-O staining and gene expression analysis. Phenotypic analyses of high-fat diet (HFD)-induced obesity in Smad3 KO mice compared to WT controls were performed. TGF-beta/Smad3 signaling was elevated in WAT from ob/ob mice compared to the controls. TGF-beta significantly inhibited adipogenesis in MEF, but the inhibitory effects of TGF-beta on adipogenesis were partially abolished in MEF from Smad3 KO mice. TGF-beta inhibited adipogenesis independent from the Wnt and beta-catenin pathway. Smad3 KO mice were protected against HFD-induced insulin resistance. The size of adipocytes from Smad3 KO mice on the HFD was significantly smaller compared to the controls. In conclusion, the TGF-beta/Smad3 signaling pathway plays key roles not only in adipogenesis but also in development of insulin resistance. (C) 2011 Elsevier Inc. All rights reserved.