PRDM16控制着一个棕色脂肪/骨肌肉开关
Patrick Seale1, Bryan Bjork, Wenli Yang
1Dana-Farber Cancer Institute and the Department of Cell Biology, Harvard Medical School, 1 Jimmy Fund Way, Boston, Massachusetts 02115, USA.
Nature
|August 23, 2008
概括
棕色脂肪细胞起源于表达肌肉基因Myf5的前体. 调节器PRDM16控制细胞命运,在棕色脂肪和肌肉发育之间切换,这对能量消耗和肥胖保护至关重要.
科学领域:
- 细胞生物学 细胞生物学
- 代谢过程中的代谢.
- 发展生物学 发展生物学
背景情况:
- 棕色脂肪组织 (BAT) 增加能量消耗,并通过脱呼吸来对抗肥胖.
- 棕色脂肪细胞的发育起源及其与其他细胞类型的关系仍然不完全理解.
研究的目的:
- 为了识别棕色脂肪细胞的细胞前体.
- 阐明转录调节器PRDM16在棕色脂肪发育和细胞命运决定中的作用.
主要方法:
- 在体内的命运映射可以追踪棕色脂肪细胞的起源.
- 在前体细胞中对PRDM16进行基因操纵 (损失和异位表达).
- 对基因表达和细胞形态学的分析.
主要成果:
- 棕色脂肪细胞与白色脂肪细胞不同,起源于表达myogenic基因Myf5.5的前体.
- PRDM16充当一个关键的开关,指导棕色脂肪生成和骨肌形成之间的细胞命运.
- 棕色脂肪前体中PRDM16的损失导致肌肉分化,而其在细胞内细胞外表达诱导棕色脂肪细胞分化.
- PRDM16与PPAR-gamma相互作用,促进棕色脂肪生成.
- 缺乏Prdm16的棕色脂肪表现出改变的形态,降低了发热基因表达,增加了肌肉特异性基因表达.
结论:
- PRDM16指明了从表达神经细胞标记的祖先的棕色脂肪血统.
- PRDM16在调节棕色脂肪发育和肌肉分化之间的平衡方面发挥着关键作用.
- 这些发现为棕色脂肪组织的发育起源及其在能量代谢中的作用提供了新的见解.
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