Mechanism of metabolic disorders caused by chronic sleep disturbance

• Project/Area Number: 18K11047
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: The University of Tokushima
• Principal Investigator: CHIKAHISA Sachiko 徳島大学, 大学院医歯薬学研究部(医学域), 講師 (00452649)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 慢性不眠 / マスト細胞 / 行動調節 / 社会性行動 / 不眠 / 代謝異常

Outline of Final Research Achievements

We investigated the mechanism of metabolic disorders associated with chronic sleep disturbance. Chronic sleep disturbance induces impaired glucose tolerance in wild-type mice, but the impaired glucose tolerance induced by sleep loss was attenuated in mice lacking mast cells throughout the body. These results suggest that mast cells are likely to be involved in metabolic disorders associated with chronic sleep disturbance. Furthermore, we demonstrated that intracranial mast cells are also involved in behavioral regulation such as social behavior via the serotonin system.

Academic Significance and Societal Importance of the Research Achievements

日本には慢性的な睡眠不足を抱えている人が多く、それに伴う肥満や糖尿病などのリスク増大が社会問題となっている。しかしながら、慢性不眠がどのように代謝性疾患を惹起するかについて、その分子メカニズムは明らかではない。本研究は、慢性不眠に伴う代謝性疾患の分子メカニズムを、マスト細胞との関連から解明しようと試みたものである。
また、近年、マスト細胞が情動行動などの行動調節に関与することが明らかとなっていることから、本研究結果は、これまで知られていない頭蓋内マスト細胞の役割を解明するものであり、代謝性疾患だけでなく、睡眠障害に併発する他の行動異常や精神疾患に関わる新たな治療法につながるものと考えられる。

Research Products

• [Journal Article] Intracranial mast cells contribute to the control of social behavior in male mice (2021)
  • Author(s): Tanioka Daisuke、Chikahisa Sachiko、Shimizu Noriyuki、Shiuchi Tetsuya、Sakai Noriaki、Nishino Seiji、Sei Hiroyoshi
  • Journal Title: Behavioural Brain Research Volume: 403 Pages: 113143-113143
  • DOI: 10.1016/j.bbr.2021.113143
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] ケトン体代謝と睡眠の最新知見 (2020)
  • Author(s): 近久幸子
  • Journal Title: 食と医療 Volume: 15 Pages: 28-35
• [Journal Article] Sleep profile during fasting in PPAR-alpha knockout mice (2020)
  • Author(s): Kondo Yoshitsugu、Chikahisa Sachiko、Shiuchi Tetsuya、Shimizu Noriyuki、Tanioka Daisuke、Uguisu Haruo、Sei Hiroyoshi
  • Journal Title: Physiology & Behavior Volume: 214 Pages: 112760-112760
  • DOI: 10.1016/j.physbeh.2019.112760
  • Peer Reviewed
• [Journal Article] Rotigotine suppresses sleep-related muscle activity augmented by injection of dialysis patients’ sera in a mouse model of restless legs syndrome (2019)
  • Author(s): Muramatsu Kazuhiro、Chikahisa Sachiko、Shimizu Noriyuki、Sei Hiroyoshi、Inoue Yuichi
  • Journal Title: Scientific Reports Volume: 9 Issue: 1 Pages: 16344-16344
  • DOI: 10.1038/s41598-019-52735-z
  • NAID: 120006875659
  • Peer Reviewed
• [Journal Article] Dopamine stimulation of the septum enhances exercise efficiency during complicated treadmill running in mice. (2019)
  • Author(s): Shiuchi Tetsuya、Masuda Takuya, Shimizu Noriyuki, Chikahisa Sachiko, Sei Hiroyoshi.
  • Journal Title: J Physiol Sci. Volume: 69 Issue: 6 Pages: 1019-1028
  • DOI: 10.1007/s12576-019-00722-4
  • NAID: 40022094103
  • Peer Reviewed
• [Journal Article] Role of orexin in exercise-induced leptin sensitivity in the mediobasal hypothalamus of mice (2019)
  • Author(s): Shiuchi Tetsuya、Miyatake Yumiko、Otsuka Airi、Chikahisa Sachiko、Sakaue Hiroshi、Sei Hiroyoshi
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 514 Issue: 1 Pages: 166-172
  • DOI: 10.1016/j.bbrc.2019.04.145
  • NAID: 120006881396
  • Peer Reviewed / Open Access
• [Journal Article] Sufficient intake of high-fat food attenuates stress-induced social avoidance behavior. (2019)
  • Author(s): Otsuka A, Shiuchi T, Chikahisa S, Shimizu N, Sei H.
  • Journal Title: Life Sci. Volume: 219 Pages: 219-230
  • DOI: 10.1016/j.lfs.2019.01.012
  • Peer Reviewed
• [Journal Article] Enhancement of fear learning in PPARα knockout mice. (2019)
  • Author(s): Chikahisa S, Chida D, Shiuchi T, Harada S, Shimizu N, Otsuka A, Tanioka D, Sei H.
  • Journal Title: Behav Brain Res. Volume: 359 Pages: 664-670
  • DOI: 10.1016/j.bbr.2018.09.020
  • Peer Reviewed
• [Journal Article] 睡眠負債と代謝性疾患 (2018)
  • Author(s): 近久幸子
  • Journal Title: 睡眠医療 Volume: 12 Pages: 369-373
• [Presentation] Sleep loss impairs glucose tolerance in mice (2020)
  • Author(s): Chikahisa S
  • Organizer: Orofacial Pain Association of the Philippines
  • Int'l Joint Research / Invited
• [Presentation] 絶食時の覚醒調節におけるPPAR-alphaおよびケトン体の役割 (2020)
  • Author(s): 近久幸子，近藤慶承，志内哲也，清水紀之，谷岡大輔，勢井宏義
  • Organizer: 第97回日本生理学会大会
• [Presentation] Chronic mild stress increases aggressive behavior in mice, (2019)
  • Author(s): Chikahisa S, Shiuchi T, Tanioka D, Shimizu N, Otsuka A, Sei H,
  • Organizer: FAOPS 2019
  • Int'l Joint Research
• [Presentation] ケトン体代謝と睡眠調節 (2019)
  • Author(s): 近久幸子
  • Organizer: 第6 回時間栄養科学研究会
  • Invited
• [Presentation] 慢性睡眠制限で生じる耐糖能異常の機序 (2018)
  • Author(s): 近久幸子，西野精治，勢井宏義
  • Organizer: 日本睡眠学会第43回定期学術集会
  • Invited
• [Book] 睡眠学 第2版，第4章：睡眠・覚醒調節の液性機構，4.3アデノシン (2020)
  • Author(s): 近久幸子（分担）
  • Total Pages: 712
  • Publisher: 朝倉書店
  • ISBN: 4254301200