Premium
Contribution of PPARα and Ketone Body to Sleep Homeostasis in Mice
Author(s) -
Chikahisa Sachiko,
Shimizu Noriyuki,
Shiuchi Tetsuya,
Sei Hiroyoshi
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.1035.4
Subject(s) - endocrinology , ketogenesis , medicine , ketone bodies , energy homeostasis , glucose homeostasis , sleep deprivation , homeostasis , chemistry , sleep (system call) , agonist , receptor , biology , metabolism , diabetes mellitus , circadian rhythm , insulin resistance , computer science , operating system
Sleep and energy metabolism have been known to share common regulatory mechanisms. Sleep restriction leads to metabolic disorders such as obesity and diabetes. However, the mechanisms of the relationships between sleep restriction and metabolic disorders have remained elusive. We have recently found that peroxisome proliferator‐activated receptors alpha (PPARα), a transcriptional factors belonging to the nuclear receptor, is involved in the regulation of sleep homeostasis. Chronic treatment of bezafibrate, a PPARs agonist enhanced the slow‐wave activity (SWA) in non‐rapid eye movement (NREM) sleep in mice. In the bezafibrate‐treated mice, plasma concentration of acetoacetate (AcAc) was increased while β‐hydroxybutyrate (BHB) was decreased. Ketogenesis is modulated by the activity of PPARα under the condition of low glucose availability. To investigate the specific effects of ketone bodies on sleep homeostasis, plasma concentration of ketone bodies were measured after sleep deprivation for 6 hours. Sleep deprivation increased plasma ketone bodies (both AcAc and BHB) and increased mRNA expression of PPARα and mitochondrial 3‐hydroxy‐3‐methylglutaryl CoA synthase 2 (Hmgcs2), a rate‐limiting enzymes of ketogenesis, in the hypothalamus and cortex. In addition, central injection of AcAc, but not BHB, increased SWA during NREM sleep and suppressed glutamate release. These results suggest that central PPARα and ketone body metabolism play a significant role in the interaction of lipid metabolism and sleep homeostasis.