PPARα is a potential therapeutic target of drugs to treat circadian rhythm sleep disorders

Hidenori Shirai, Katsutaka Oishi, Takashi Kudo, Shigenobu Shibata, Norio Ishida

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Recent progress at the molecular level has revealed that nuclear receptors play an important role in the generation of mammalian circadian rhythms. To examine whether peroxisome proliferator-activated receptor alpha (PPARα) is involved in the regulation of circadian behavioral rhythms in mammals, we evaluated the locomotor activity of mice administered with the hypolipidemic PPARα ligand, bezafibrate. Circadian locomotor activity was phase-advanced about 3 h in mice given bezafibrate under light-dark (LD) conditions. Transfer from LD to constant darkness did not change the onset of activity in these mice, suggesting that bezafibrate advanced the phase of the endogenous clock. Surprisingly, bezafibrate also advanced the phase in mice with lesions of the suprachiasmatic nucleus (SCN; the central clock in mammals). The circadian expression of clock genes such as period2, BMAL1, and Rev-erbα was also phase-advanced in various tissues (cortex, liver, and fat) without affecting the SCN. Bezafibrate also phase-advanced the activity phase that is delayed in model mice with delayed sleep phase syndrome (DSPS) due to a Clock gene mutation. Our results indicated that PPARα is involved in circadian clock control independently of the SCN and that PPARα could be a potent target of drugs to treat circadian rhythm sleep disorders including DSPS.

Original languageEnglish
Pages (from-to)679-682
Number of pages4
JournalBiochemical and Biophysical Research Communications
Volume357
Issue number3
DOIs
Publication statusPublished - 2007 Jun 8

Keywords

  • Bezafibrate
  • Circadian rhythm
  • Clock gene
  • Delayed sleep phase syndrome (DSPS)
  • PPARα
  • Suprachiasmatic nucleus

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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