FEEDING-INDUCED RAPID RESETTING OF THE HEPATIC CIRCADIAN CLOCK IS ASSOCIATED WITH ACUTE INDUCTION OF PER2 AND DEC1 TRANSCRIPTION IN RATS

Abstract

The synchronization of the master clock to photic cues is associated with a rapid induction of Per1, which plays an important role in initiating light-induced circadian resetting. However, the transcriptional mechanisms of clock gene expression in food-entrainable peripheral clocks have not been fully assessed. To understand how food cues might entrain a mammalian peripheral clock, we examined the responses in the expression of clock genes in rat livers to different feeding stimuli. The food-entrainable liver clock is more flexible than the light-entrainable SCN clock and can be reset rapidly at any time of day. A 30 min feeding stimulus was sufficient to significantly induce the expression of Per2 and Dec1 within 1 h and alter the transcript levels and circadian phases of other selected clock genes (Bmal1, Cry1, Per1, Per3, Dec2, and Rev-erba) in the liver clock at longer time intervals. Moreover, among the examined clock genes, Per2 was most sensitive to food cues, which could be significantly induced by a minimal amount of food. Furthermore, in contrast to the other hepatic clock genes, the feeding reversal-induced 12 h phase shift of Per2 could be rapidly and consistently accomplished, regardless of the shift of the light/dark cycle. In conclusion, the feeding-induced resetting of the circadian clock in the liver is associated with the acute induction of Per2 and Dec1 transcription, which may serve as the main and secondary input regulators that initiate this feeding-induced circadian resetting. (Author correspondence: [email protected])

Keywords:

• Liver
• Short-term feeding
• Rapid response
• Circadian clock resetting
• Daytime restricted feeding

ACKNOWLEDGMENTS

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.