Influence of a time-restricted feeding schedule on the daily rhythm of abcb1a gene expression and its function in rat intestine

J Pharmacol Exp Ther. 2010 Nov;335(2):418-23. doi: 10.1124/jpet.110.170837. Epub 2010 Jul 28.

Abstract

P-glycoprotein (P-gp) is one of the ATP-binding cassette transporters and acts as an efflux pump for cytotoxic substances. P-gp mRNA expression and transporting activity show the daily rhythm and contribute to the chrono-pharmacokinetic profiles of many drugs. It is reported that the daily rhythm of abcb1a mRNA is regulated by a circadian clock-controlled output pathway. Time-restricted feeding is well known to shift the peripheral circadian phase of clock gene expression without changing the central clock function. This study was undertaken to examine the influence of a time-restricted feeding procedure during the light phase on the daily rhythms of abcb1a mRNA expression and P-gp activity. The abcb1a mRNA and P-gp activity showed a daily rhythm with a peak early in the dark phase in rat intestine under ad libitum feeding. Time-restricted feeding during the light phase shifted these rhythms to 12-h advance. The mRNA expression of clock genes (DBP and HLF, the transcript activators of abcb1a) also showed daily rhythms, and their phases were shifted by the time-restricted feeding procedure. The peak time of DBP mRNA expression was similar to that of abcb1a mRNA expression under ad libitum feeding and time-restricted feeding conditions. These results indicate that a time-restricted feeding procedure changes DBP mRNA expression, which in turn influences abcb1a mRNA expression and P-gp activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / genetics*
  • ATP Binding Cassette Transporter, Subfamily B / metabolism
  • ATP Binding Cassette Transporter, Subfamily B / physiology
  • Animals
  • Biological Transport
  • Circadian Rhythm / genetics*
  • Corticosterone / blood
  • Digoxin / pharmacokinetics
  • Eating / genetics*
  • Gene Expression*
  • Jejunum / metabolism*
  • Male
  • Perfusion
  • RNA, Messenger / genetics
  • Rats
  • Rats, Wistar
  • Reverse Transcriptase Polymerase Chain Reaction
  • Substrate Specificity

Substances

  • ATP Binding Cassette Transporter, Subfamily B
  • RNA, Messenger
  • Digoxin
  • multidrug resistance protein 3
  • Corticosterone