Bezafibrate, a peroxisome proliferator-activated receptors agonist, decreases body temperature and enhances electroencephalogram delta-oscillation during sleep in mice.
Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors belonging to the nuclear receptor family. PPARs play a critical role in lipid and glucose metabolism. We examined whether chronic treatment with bezafibrate, a PPAR agonist, would alter sleep and body temperature (BT). Mice fed with a control diet were monitored for BT, electroencephalogram (EEG), and electromyogram for 48 h under light-dark conditions. After obtaining the baseline recording, the mice were provided with bezafibrate-supplemented food for 2 wk, after which the same recordings were performed. Two-week feeding of bezafibrate decreased BT, especially during the latter half of the dark period. BT rhythm and sleep/wake rhythm were phase advanced about 2-3 h by bezafibrate treatment. Bezafibrate treatment also increased the EEG delta-power in nonrapid eye movement sleep compared with the control diet attenuating its daily amplitude. Furthermore, bezafibrate-treated mice showed no rebound of EEG delta-power in nonrapid eye movement sleep after 6 h sleep deprivation, whereas values in control mice largely increased relative to baseline. DNA microarray, and real-time RT-PCR analysis showed that bezafibrate treatment increased levels of Neuropeptide Y mRNA in the hypothalamus at both Zeitgeber time (ZT) 10 and ZT22, and decreased proopiomelanocortin-alpha mRNA in the hypothalamus at ZT10. These findings demonstrate that PPARs participate in the control of both BT and sleep regulation, which accompanied changes in gene expression in the hypothalamus. Activation of PPARs may enhance deep sleep and improve resistance to sleep loss.
Chikahisa
Sachiko
S
Department of Integrative Physiology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8503, Japan.
Tominaga
Kumiko
K
Kawai
Tomoko
T
Kitaoka
Kazuyoshi
K
Oishi
Katsutaka
K
Ishida
Norio
N
Rokutan
Kazuhito
K
Séi
Hiroyoshi
H
D000818:Animals; D001629:Bezafibrate / Q000494:pharmacology*; D001831:Body Temperature / Q000187:drug effects*; D001833:Body Temperature Regulation / Q000187:drug effects; D003700:Delta Rhythm / Q000187:drug effects*; D015870:Gene Expression / Q000187:drug effects; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D007031:Hypothalamus / Q000187:drug effects / Q000502:physiology; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009478:Neuropeptide Y / Q000235:genetics / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists; D011333:Pro-Opiomelanocortin / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012894:Sleep Stages / Q000187:drug effects*; D014851:Wakefulness / Q000187:drug effects
D000960:Hypolipidemic Agents; D009478:Neuropeptide Y; D047492:Peroxisome Proliferator-Activated Receptors; D011333:Pro-Opiomelanocortin; D001629:Bezafibrate