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

    Fingerprint

    Circadian Rhythm Sleep Disorders
    Bezafibrate
    PPAR alpha
    Clocks
    Circadian Clocks
    Mammals
    Pharmaceutical Preparations
    Locomotion
    Circadian Rhythm
    Genes
    Therapeutics
    Light
    Suprachiasmatic Nucleus
    Darkness
    Cytoplasmic and Nuclear Receptors
    Liver
    Fats
    Sleep
    Tissue
    Ligands

    Keywords

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

    ASJC Scopus subject areas

    • Biochemistry
    • Biophysics
    • Molecular Biology

    Cite this

    PPARα is a potential therapeutic target of drugs to treat circadian rhythm sleep disorders. / Shirai, Hidenori; Oishi, Katsutaka; Kudo, Takashi; Shibata, Shigenobu; Ishida, Norio.

    In: Biochemical and Biophysical Research Communications, Vol. 357, No. 3, 08.06.2007, p. 679-682.

    Research output: Contribution to journalArticle

    Shirai, Hidenori ; Oishi, Katsutaka ; Kudo, Takashi ; Shibata, Shigenobu ; Ishida, Norio. / PPARα is a potential therapeutic target of drugs to treat circadian rhythm sleep disorders. In: Biochemical and Biophysical Research Communications. 2007 ; Vol. 357, No. 3. pp. 679-682.
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