核受体LXR是一种葡萄糖传感器
Nico Mitro1, Puiying A Mak, Leo Vargas
1Genomics Institute of the Novartis Research Foundation, 10675 John Hopkins Drive, San Diego, California 92121, USA.
Nature
|December 26, 2006
概括
葡萄糖直接激活肝脏X受体 (LXR),这是脂质代谢的关键调节器. 这一发现揭示了葡萄糖如何控制自身在肝脏中的代谢命运的新奇机制.
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
- 肝病学 肝病学是一种肝病学.
背景情况:
- 肝脏在通过生产和消费来维持葡萄糖平衡中发挥着至关重要的作用.
- 胰岛素和ChREBP是已知的肝脏葡萄糖代谢和脂质生成的调节剂.
- 葡萄糖影响其自身代谢命运的确切机制仍在研究中.
研究的目的:
- 研究一种新的机制,通过该机制葡萄糖调节自己的新陈代谢命运在肝脏.
- 确定葡萄糖是否直接与肝脏X受体 (LXR) 相互作用并调节其活性.
主要方法:
- 用于测试葡萄糖和葡萄糖-6-酸盐直接结合和激活LXR-alpha和LXR-beta的生物化学测试.
- 对LXR基因对葡萄糖的反应进行基因表达分析.
- 在小鼠体内研究以评估葡萄糖饮食对胆固醇平衡基因的影响.
主要成果:
- 确定d-葡萄糖和d-葡萄糖-6-酸盐是LXR-alpha和LXR-beta的直接激动剂.
- 葡萄糖在生理性肝脏度下激活LXR,诱导目标基因表达类似于氧化.
- 在接受葡萄糖治疗的小鼠中,LXR依赖的胆固醇稳态基因的表达被上调,这证实了葡萄糖是内源的LXR连接体.
结论:
- 肝脏X受体 (LXR) 作为一个转录开关,整合肝脏葡萄糖代谢和脂肪酸合成.
- 葡萄糖直接刺激LXR,提供葡萄糖可用性和脂质代谢之间的新分子联系.
- 这项研究揭示了以前未知的肝脂合成葡萄糖调节的途径.
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