Glucose down-regulates Per1 and Per2 mRNA levels and induces circadian gene expression in cultured rat-1 fibroblasts

Tsuyoshi Hirota, Toshiyuki Okano, Koichi Kokame, Hiroko Shirotani-Ikejima, Toshiyuki Miyata, Yoshitaka Fukada

Research output: Contribution to journalArticlepeer-review

252 Citations (Scopus)

Abstract

In mammals, peripheral circadian clocks are present in most tissues, but little is known about how these clocks are synchronized with the ambient 24-h cycles. By using rat-1 fibroblasts, a model cell system of the peripheral clock, we found that an exchange of the culture medium triggered circadian gene expression that was preceded by slow down-regulation of Per1 and Per2 mRNA levels. This profile contrasts to the immediate up-regulation of these genes often observed for clock resetting. The screening of factor(s) responsible for the down-regulation revealed glucose as a key component triggering the circadian rhythm. The requirement of both glucose metabolism and RNA/protein synthesis for the down-regulation suggests the involvement of gene(s) immediately up-regulated by glucose metabolism. An analysis with high density oligonucleotide microarrays identified >100 glucose-regulated genes. We found among others immediately up-regulated genes encoding transcriptional regulators TIEG1, VDUP1, and HES1, in addition to cooperatively regulated genes that are associated with cholesterol biosynthesis and cell cycle. The immediate up-regulation of Tieg1 and Vdup1 expression was dependent on glucose metabolism but not on protein synthesis, suggesting that the transcriptional regulators mediate the glucose-induced down-regulation of Per1 and Per2 expression. These results illustrate a novel mode of peripheral clock resetting by external glucose, a major food metabolite.

Original languageEnglish
Pages (from-to)44244-44251
Number of pages8
JournalJournal of Biological Chemistry
Volume277
Issue number46
DOIs
Publication statusPublished - 2002 Nov 15

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Glucose down-regulates Per1 and Per2 mRNA levels and induces circadian gene expression in cultured rat-1 fibroblasts'. Together they form a unique fingerprint.

Cite this