通过Zfp42323进行前脂肪细胞确定的转录控制
Rana K Gupta1, Zoltan Arany, Patrick Seale
1Department of Cancer Biology and Division of Metabolism and Chronic Disease, Dana-Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Nature
|March 5, 2010
概括
研究人员确定了指蛋白Zfp423作为脂肪细胞发育的关键调节者. 这一发现通过了解前脂肪细胞的决定,为肥胖和能量平衡提供了新的见解.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 代谢研究研究 代谢研究
背景情况:
- 肥胖是一个全球性的健康危机,需要对能量平衡和脂肪细胞 (脂肪细胞) 发育有更深入的了解.
- 前脂肪细胞分化成脂肪细胞是由PPARgamma调节的,但上游的分子机制仍然不清楚.
研究的目的:
- 确定参与前脂肪细胞确定的新型转录因子.
- 阐明Zfp423在脂肪生成中的作用及其调节机制.
主要方法:
- 对转录元件的定量分析,以确定前脂质纤维细胞中的丰富因素.
- 细胞系中Zfp423的子宫外表达和shRNA介导的淘汰 (NIH 3T3,3T3-L1).
- 分析Zfp423缺乏的小鼠胚胎中的脂肪细胞分化.
主要成果:
- 鉴定Zfp423是一种指蛋白,富含在前脂质纤维细胞中.
- 异位Zfp423表达诱导了NIH 3T3细胞中的脂肪细胞分化,通过激活PPARgamma.
- 降低Zfp423水平导致3T3-L1细胞和小鼠胚胎中的Pparg表达和脂肪生成受损.
- Zfp423扩大了BMP信号,取决于其SMAD结合能力,以调节Pparg.
结论:
- Zfp423是预脂细胞决定的关键转录调节器.
- Zfp423在白色和棕色脂肪细胞分化中起着重要作用.
- 这一发现促进了对控制脂肪细胞发育和能量恒温的分子途径的理解.
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