Prediction of preadipocyte differentiation by gene expression reveals role of insulin receptor substrates and necdin
Prediction of preadipocyte differentiation by gene expression reveals role of insulin receptor substrates and necdin
复制标题
DOI：
10.1038/ncb1259
复制
发表时间：
2005-06-01
影响因子：
21.3
通讯作者：
Kahn, CR
中科院分区：
文献类型：
--
作者：
Tseng, YH;Butte, AJ;Kahn, CR
胰岛素/IGF-1（胰岛素样生长因子1）信号通路通过复杂的信号网络促进脂肪细胞分化。在这里，使用来自野生型和胰岛素受体底物（IRS）敲除动物表现出渐进性受损分化的棕色前脂肪细胞的微阵列分析，我们定义了374个基因/表达序列标签，其在前脂肪细胞中的表达与细胞分化的最终能力相关。这些基因中的许多，包括前脂肪细胞因子-1（Pref-1）和Wnt信号通路的多个成员，与早期脂肪形成事件有关。在Irs敲除的不能分化的细胞中，Necdin也显著增加，并且necdin的敲低通过下调Pref-1和Wnt 10a表达恢复棕色脂肪形成。胰岛素受体底物蛋白调节necdin-E2 F4相互作用，通过环AMP反应元件结合蛋白（CREB）依赖性途径抑制过氧化物酶体增殖物激活受体γ（PPAR γ）转录。这些共同定义了一个关键的信号网络，参与棕色前脂肪细胞的确定。
The insulin/IGF-1 (insulin-like growth factor 1) signalling pathway promotes adipocyte differentiation via complex signalling networks. Here, using microarray analysis of brown preadipocytes that are derived from wild-type and insulin receptor substrate (Irs) knockout animals that exhibit progressively impaired differentiation, we define 374 genes/expressed-sequence tags whose expression in preadipocytes correlates with the ultimate ability of the cells to differentiate. Many of these genes, including preadipocyte factor-1 (Pref-1) and multiple members of the Wnt signalling pathway, are related to early adipogenic events. Necdin is also markedly increased in Irs knockout cells that cannot differentiate, and knockdown of necdin restores brown adipogenesis with downregulation of Pref-1 and Wnt10a expression. Insulin receptor substrate proteins regulate a necdin-E2F4 interaction that represses peroxisome-proliferator-activated receptor gamma (PPAR gamma) transcription via a cyclic AMP response element binding protein (CREB)-dependent pathway. Together these define a key signalling network that is involved in brown preadipocyte determination.