Effects of restricted feeding on daily fluctuations of hepatic functions including p450 monooxygenase activities in rats.
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.
Hirao
Jun
J
Medicinal Safety Research Laboratories, Sankyo Co., Ltd., 717, Horikoshi, Fukuroi, Shizuoka 437-0065, Japan. jhirao@sankyo.co.jp
Arakawa
Shingo
S
Watanabe
Kyoko
K
Ito
Kazumi
K
Furukawa
Tadashi
T
D015660:7-Alkoxycoumarin O-Dealkylase / Q000096:biosynthesis; D000818:Animals; D001835:Body Weight; D002940:Circadian Rhythm; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D005508:Food Deprivation; D020869:Gene Expression Profiling; D008027:Light; D008099:Liver / Q000201:enzymology*; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D009991:Oscillometry; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013493:Suprachiasmatic Nucleus / Q000201:enzymology; D013997:Time Factors; D014158:Transcription, Genetic
D012333:RNA, Messenger; D012313:RNA; D003577:Cytochrome P-450 Enzyme System; D015660:7-Alkoxycoumarin O-Dealkylase