Zhou Yuanfei, Song Tongxing, Peng Jie, Zhou Zheng, Wei Hongkui, Zhou Rui, Jiang Siwen, Peng Jian
State Key Laboratory of Agricultural Microbiology, Division of Animal Infectious Disease, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, P. R. China.
Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, P. R. China.
Oncotarget. 2016 Nov 22;7(47):77707-77720. doi: 10.18632/oncotarget.12774.
Sirtuin 1 (SIRT1) regulates adipocyte and osteoblast differentiation. However, the underlying mechanism should be investigated. This study revealed that SIRT1 acts as a crucial repressor of adipogenesis. RNA-interference-mediated SIRT1 knockdown or genetic ablation enhances adipogenic potential, whereas SIRT1 overexpression inhibits adipogenesis in mesenchymal stem cells (MSCs). SIRT1 also deacetylates the histones of sFRP1, sFRP2, and Dact1 promoters; inhibits the mRNA expression of sFRP1, sFRP2, and Dact1; activates Wnt signaling pathways; and suppresses adipogenesis. SIRT1 deacetylates β-catenin to promote its accumulation in the nucleus and thus induces the transcription of genes that block MSC adipogenesis. In mice, the partial absence of SIRT1 promotes the formation of white adipose tissues without affecting the development of the body of mice. Our study described the regulatory role of SIRT1 in Wnt signaling and proposed a regulatory mechanism of adipogenesis.
沉默调节蛋白1（SIRT1）调节脂肪细胞和成骨细胞的分化。然而，其潜在机制仍有待研究。本研究表明，SIRT1是脂肪生成的关键抑制因子。RNA干扰介导的SIRT1敲低或基因敲除可增强脂肪生成潜能，而SIRT1过表达则抑制间充质干细胞（MSC）的脂肪生成。SIRT1还可使分泌型卷曲相关蛋白1（sFRP1）、分泌型卷曲相关蛋白2（sFRP2）和Dapper1（Dact1）启动子的组蛋白去乙酰化；抑制sFRP1、sFRP2和Dact1的mRNA表达；激活Wnt信号通路；并抑制脂肪生成。SIRT1使β-连环蛋白去乙酰化，促进其在细胞核中的积累，从而诱导阻断MSC脂肪生成的基因转录。在小鼠中，SIRT1部分缺失可促进白色脂肪组织的形成，而不影响小鼠身体的发育。我们的研究描述了SIRT1在Wnt信号通路中的调节作用，并提出了脂肪生成的调节机制。
