核受体的冷诱导性联合激活剂与适应性热生成有关
1Dana-Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Cell
|April 7, 1998
概括
研究人员发现PGC-1,一种激活适应性热生成的蛋白质,身体的热量产生. 这一发现对于理解能量平衡和发展肥胖防御是至关重要的.
科学领域:
- 代谢调节 代谢调节 代谢调节
- 分子生物学分子生物学
- 肥胖研究的研究.
背景情况:
- 适应性热生成对于能量恒温和预防肥胖至关重要.
- 了解热生成的分子机制是代谢疾病研究的关键.
研究的目的:
- 确定参与适应性热生成的新型转录协活性剂.
- 阐明PGC-1在调节发热基因中的作用.
主要方法:
- 从棕色脂肪组织cDNA中克隆一种新的转录协活性剂PGC-1.
- 分析pgc-1mRNA表达的反应冷暴露在小鼠.
- 评估PGC-1对解蛋白1 (UCP-1) 促进剂活性的影响.
- 评估PGC-1对白色脂肪细胞中的基因表达和线粒体生物发生的影响.
主要成果:
- 在暴露于寒冷后,PGC-1 mRNA水平在棕色脂肪和骨肌肉中显著增加.
- PGC-1增强了PPARgamma和甲状腺激素受体在UCP-1促进器上的转录活性.
- 在白色脂肪细胞中异位PGC-1表达会诱导UCP-1和线粒体呼吸链酶.
- PGC-1增加了脂肪细胞中的线粒体DNA含量.
结论:
- PGC-1作为一个关键的联合激活剂,将核受体与适应性热生成的转录控制联系起来.
- 这一发现为针对肥胖和代谢功能障碍的干预提供了一个分子标.
- PGC-1在调解对寒冷暴露的代谢适应方面发挥着重要作用.
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