Abstract
Hepatic P450 monooxygenase activities, assessed by measurement of 7-alkoxycoumarin O-dealkylase (ACD) activities, show obvious daily fluctuations in male rats with high values during the dark period and low values during the light period. We have already confirmed that the ACD activities are controlled by the suprachiasmatic nucleus (SCN), which is well known as the oscillator of circadian rhythm. Recently, it is reported that circadian oscillators exist not only in the SCN but also in peripheral organs. To date, it is unclear which circadian oscillators predominantly drive the daily fluctuations of hepatic ACD activities. To address this question, we examined the effects of restricted feeding, which uncouples the circadian oscillators in the liver from the central pacemaker in the SCN, on the daily fluctuations in hepatic ACD activities in male rats. Here we show that restricted feeding inverts the oscillation phase of the daily fluctuations in hepatic ACD activities. Regarding the hepatic P450 content, there were no fluctuations between the light and dark periods under ad libitum and restricted feeding conditions. Therefore, it is considered that the daily fluctuations in hepatic ACD activities are predominantly driven by the circadian factors in peripheral organs rather than by the oscillator in the SCN directly.
Highlights
Liver but are ineffective for resetting the time of the central oscillator [10, 11]
We examined the effects of restricted feeding during the light period on the daily fluctuations in hepatic alkoxycoumarin O-dealkylase (ACD) activities in male rats
The daily fluctuations are under the control of the central oscillator in the suprachiasmatic nucleus (SCN), since SCN lesions completely eliminate the fluctuation while shifting feeding conditions from ad libitum to fasting dose not [17, 18]
Summary
Liver but are ineffective for resetting the time of the central oscillator [10, 11]. restricted feeding during the light period can completely uncouple the peripheral oscillators from the central oscillator in nocturnal rodents such as rats and mice. The ACD activities in the liver show obvious daily fluctuations in male rats with high values during the dark period and low values during the light period [17,18,19]. The daily fluctuations are observed under ad libitum feeding conditions and under fasting conditions [17] These results indicate that the central oscillator in the SCN controls the daily fluctuations in hepatic ACD activities. To address this question, we examined the effects of restricted feeding during the light period on the daily fluctuations in hepatic ACD activities in male rats. We investigated the effects of restricted feeding on the gene expression profiles of periodic genes in the liver to understand the underlying mechanism using microarray
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