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 language | English |
|---|---|
| Pages (from-to) | 679-682 |
| Number of pages | 4 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 357 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 2007 Jun 8 |
Fingerprint
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 journal › Article
}
TY - JOUR
T1 - PPARα is a potential therapeutic target of drugs to treat circadian rhythm sleep disorders
AU - Shirai, Hidenori
AU - Oishi, Katsutaka
AU - Kudo, Takashi
AU - Shibata, Shigenobu
AU - Ishida, Norio
PY - 2007/6/8
Y1 - 2007/6/8
N2 - 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.
AB - 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.
KW - Bezafibrate
KW - Circadian rhythm
KW - Clock gene
KW - Delayed sleep phase syndrome (DSPS)
KW - PPARα
KW - Suprachiasmatic nucleus
UR - http://www.scopus.com/inward/record.url?scp=34247467864&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34247467864&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2007.04.002
DO - 10.1016/j.bbrc.2007.04.002
M3 - Article
C2 - 17449013
AN - SCOPUS:34247467864
VL - 357
SP - 679
EP - 682
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 3
ER -