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The hepatic circadian clock modulates xenobiotic metabolism in mice
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DeBruyne, Jason P., Weaver, D. R. and Dallmann, Robert (2014) The hepatic circadian clock modulates xenobiotic metabolism in mice. Journal of Biological Rhythms, 29 (4). pp. 277-287. doi:10.1177/0748730414544740
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Official URL: http://dx.doi.org/10.1177/0748730414544740
Abstract
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.
| Item Type: | Journal Article | ||||
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| Divisions: | Faculty of Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Metabolic and Vascular Health (- until July 2016) Faculty of Medicine > Warwick Medical School |
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| Journal or Publication Title: | Journal of Biological Rhythms | ||||
| Publisher: | Sage Publications Ltd. | ||||
| ISSN: | 0748-7304 | ||||
| Official Date: | August 2014 | ||||
| Dates: |
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| Volume: | 29 | ||||
| Number: | 4 | ||||
| Page Range: | pp. 277-287 | ||||
| DOI: | 10.1177/0748730414544740 | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Access rights to Published version: | Restricted or Subscription Access |
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