Bezafibrate, a Peroxisome Proliferator-Activated Receptors Agonist, Decreases Body Temperature and Enhances Electroencephalogram Delta-Oscillation during Sleep in Mice
Abstract
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-α 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.
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In a mouse model, bezafibrate, a PPAR-α agonist, affects baseline sleep and recovery sleep after sleep restriction.
“Bezafibrate, an antihyperlipidemic PPAR-α agonist, has been shown in a mouse model to affect both BL sleep, with increased EEG δ-power, and recovery sleep following sleep restriction, with a reduced rebound in EEG δ-power (49).”
From Oxalic acid and diacylglycerol 36:3 are cross-species markers of sleep debt (2015) · cites this paper as [49]
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Fibroblast growth factor 21 and its relationship with central precocious puberty in girls
Hao, X., Wang, J., Zhou, R., Sun, M., & Cheng, Y. (2026) · Endocrine Connections · doi:10.1530/ec-26-0320
- Authors
- Chikahisa, S., Tominaga, K., Kawai, T., Kitaoka, K., Oishi, K., Ishida, N., Rokutan, K., & Séi, H.
- Affiliations
- Tokushima University (JP)
- National Institute of Advanced Industrial Science and Technology (JP)
- University of Tsukuba (JP)
- Departments of Integrative Physiology (S.C., H.S.), Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8503, Japan
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2008-09-11
- Volume
- 149
- Issue
- 10
- Pages
- 5262-5271
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W2091371379
- Cited by
- 57
- References
- 42
- Citations by year
- 2026: 1 · 2023: 3 · 2022: 4 · 2021: 5 · 2020: 2 · 2019: 3 · 2018: 3 · 2017: 1 · 2016: 3 · 2015: 6 · 2014: 3 · 2013: 6 · 2012: 2
- FWCI
- 2.23
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Tokushima
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- bezafibrate, peroxisome proliferator-activated receptors, body temperature, sleep regulation, EEG delta power, NREM sleep, sleep deprivation, hypothalamus, neuropeptide Y, circadian rhythm, phase advance, PPAR agonists
- MeSH terms
- Animals, Hypolipidemic Agents, Bezafibrate, Body Temperature, Body Temperature Regulation, Delta Rhythm, Hypothalamus, Injections, Intraventricular, Male, Mice, Inbred ICR, Neuropeptide Y, Pro-Opiomelanocortin, Sleep Stages, Wakefulness, Gene Expression, Reverse Transcriptase Polymerase Chain Reaction, Oligonucleotide Array Sequence Analysis, Peroxisome Proliferator-Activated Receptors, Mice
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