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肥胖和新陈代谢综合征在昼夜活动时钟突变小鼠

Fred W Turek¹, Corinne Joshu, Akira Kohsaka

¹Department of Neurology, Northwestern University, Evanston, IL 60208, USA.

Science (New York, N.Y.)

|April 23, 2005

概括

生物钟基因CLOCK对于调节食节奏和预防肥胖至关重要. 破坏这个时钟会导致代谢综合征,并影响小鼠的能量平衡.

科学领域:

神经科学是一个神经科学.
代谢过程中的代谢.
时间生物学时间生物学

背景情况:

CLOCK转录因子是上性核中的分子昼夜钟的组成部分.
昼夜节律显著影响生理过程,包括能量平衡.

研究的目的:

研究CLOCK基因在调节白天食模式和代谢健康中的作用.
确定时钟基因突变对能量平衡和相关的下丘脑的影响.

主要方法:

使用同卵性时钟突变小鼠和野生类型的 littermates进行比较.
评估了日常食节奏,体重和代谢参数 (瘦素,脂质,葡萄糖,胰岛素).
分析了与能量恒温相关的下丘脑神经转录的表达.

主要成果:

时钟突变的小鼠表现出日间食节奏,吞过多和肥胖.
突变小鼠发展了代谢综合征,包括高脂血症,高脂血症,肝硬化症,高血糖症和低胰岛素症.
关键的下丘脑能量平衡的转录表达在钟表突变小鼠中减少.

结论:

昼夜钟基因网络,特别是CLOCK,对于维持哺乳动物的能量平衡至关重要.
CLOCK基因的干扰显著损害了代谢调节,导致肥胖和代谢综合征.
循环时钟功能对于协调食行为和代谢平衡至关重要.

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