通过PRDM16-C/EBP-β转录复合体启动肌细胞细胞转换为棕色脂肪
Shingo Kajimura1, Patrick Seale, Kazuishi Kubota
1Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, Massachusetts 02115, USA.
Nature
|July 31, 2009
概括
PRDM16和C/EBP-β形成一个复合体,改变细胞命运,从前体中产生棕色脂肪细胞. 这一发现为肥胖和2型糖尿病提供了潜在的新疗法.
科学领域:
- 细胞生物学 细胞生物学
- 代谢过程中的代谢.
- 分子生物学分子生物学
背景情况:
- 棕色脂肪细胞以热的形式消散能量,对抗感冒和肥胖.
- 众所周知,PRDM16蛋白诱导棕色脂肪的确定和分化.
- 控制棕色脂肪发育开关的精确分子机制尚不清楚.
研究的目的:
- 阐明PRDM16控制细胞命运转换为棕色脂肪的分子机制.
- 研究PRDM16在形成棕色脂肪发育的转录复合体中的作用.
- 评估PRDM16和C/EBP-β在诱导非脂肪细胞中的棕色脂肪形成方面的潜力.
主要方法:
- 研究了PRDM16和C/EBP-β之间的相互作用.
- 在纤维细胞中利用PRDM16和C/EBP-β的强制表达.
- 将工程纤维细胞移植到小鼠体内,以形成子宫外脂肪.
- 在合成棕色脂肪组织中评估葡萄糖摄取量,使用氧糖 (FDG) 的正子发射断层扫描 (PET).
主要成果:
- PRDM16与C/EBP-β (LAP) 的活性形式形成了一个转录复合体.
- 这种PRDM16-C/EBP-β复合体对于将细胞命运从肌细胞前体转换为棕色脂肪细胞至关重要.
- 强制表达PRDM16和C/EBP-β诱导了小鼠和人类纤维细胞中的功能性棕色脂肪程序.
- 移植的纤维细胞形成了宫外棕色脂肪组织,表现出类似于内源棕色脂肪的葡萄糖吸收.
结论:
- 该PRDM16-C/EBP-β复合体启动了从肌细胞前体中形成棕色脂肪的过程.
- 这种机制为棕色脂肪产生提供了一条新的途径.
- 这些发现表明,通过操纵这个复合体,对肥胖和2型糖尿病有潜在的治疗策略.
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