The hepatic circadian clock modulates xenobiotic metabolism in mice.
The hepatic circadian clock modulates xenobiotic metabolism in mice.
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DOI：
10.1177/0748730414544740
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发表时间：
2014-08
影响因子：
3.5
通讯作者：
Dallmann R
中科院分区：
文献类型：
--
作者：
DeBruyne JP;Weaver DR;Dallmann R
生物钟产生调节生理过程的基因表达的每日循环。肝脏在异种代谢中起着重要的作用，并且也被证明拥有自己的细胞时钟。肝脏时钟与大脑中的主时钟同步，即使在肝脏时钟受到抑制的情况下，机体整体的行为也可以驱动部分有节奏的基因表达。然而，到目前为止，很少有证据表明肝脏时钟在调节异种代谢方面是否具有重要的功能。因此，我们用戊巴比妥和对乙酰氨基酚刺激全身或肝脏缺乏生物钟功能的小鼠，并在一天中的不同时间分别评估戊巴比妥睡眠时间（PBST）和对乙酰氨基酚的毒性。结果表明，肝脏时钟对外源性解毒的节律变化至关重要。令人惊讶的是，生物钟被打乱的方式似乎决定了肝脏中异种代谢的速度。时钟缺陷小鼠对扑热息痛具有明显的抗性，PBST较长，而周期缺陷小鼠PBST较短。这些结果表明肝脏组织内生性外周昼夜节律振荡器在调节外源代谢中的重要作用。
The circadian clock generates daily cycles of gene expression that regulate physiological processes. The liver plays an important role in xenobiotic metabolism, and also has been shown to possess its own cell-based clock. The liver clock is synchronized by the master clock in the brain, and a portion of rhythmic gene expression can be driven by behavior of the organism as a whole even when the hepatic clock is suppressed. So far, however, there is relatively little evidence indicating whether the liver clock is functionally important in modulating xenobiotic metabolism. Thus, mice lacking circadian clock function in the whole body or specifically in liver were challenged with pentobarbital and acetaminophen, and pentobarbital sleep time (PBST) and acetaminophen toxicity, respectively, was assessed at different times of day in mutant and control mice. The results suggest that the liver clock is essential for rhythmic changes in xenobiotic detoxification. Surprisingly, it seems that the way in which the clock is disrupted determines the rate of xenobiotic metabolism in the liver. CLOCK-deficient mice are remarkably resistant to acetaminophen and exhibit a longer PBST, while PERIOD-deficient mice have a short PBST. These results indicate an essential role of the tissue-intrinsic peripheral circadian oscillator in the liver in regulating xenobiotic metabolism.
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DOI：
10.1073/pnas.1118726109
发表时间：
2012-04-03
影响因子：
11.1
作者：
Eckel-Mahan, Kristin L.;Patel, Vishal R.;Sassone-Corsi, Paolo
通讯作者：
Sassone-Corsi, Paolo
影响因子：
9.2
作者：
Akhtar, RA;Reddy, AB;Kyriacou, CP
通讯作者：
Kyriacou, CP
影响因子：
5
作者：
Khemawoot, Phisit;Nishino, Kousuke;Miyamoto, Ken-ichi
通讯作者：
Miyamoto, Ken-ichi
影响因子：
3.5
作者：
Henderson, CJ;Pass, GJ;Wolf, CR
通讯作者：
Wolf, CR
影响因子：
29
作者：
Gachon, Federic;Olela, Fabienne Fleury;Schibler, Ueli
通讯作者：
Schibler, Ueli