Effects of the orexin system on energy metabolism during sleep

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K17657
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: University of Tsukuba
• Principal Investigator: Park Insung 筑波大学, 国際統合睡眠医科学研究機構, 助教 (60812302)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: ヒューマンカロリメータ / 睡眠 / エネルギー代謝 / オレキシン / 脂肪酸化 / 間接熱量測定

Outline of Final Research Achievements

The orexin receptor antagonists such as suvorexant have been clinically approved as sleep-inducing medicine to treat insomnia. However, the role of orexin system in the regulation of energy metabolism remains unclear in humans. We assessed the effect of suvorexant (20mg) on energy metabolism during sleep and shortly after awakening in a randomized, double-blind, placebo-controlled, crossover study in 14 healthy men. Sleep architecture was not changed by suvorexant, except for an increase in rapid eye movement (REM) sleep amount and a decrease in non-REM sleep 1 amount. Unexpectedly, Suvorexant increased fat oxidation during sleep and its effect remained during the first hour after waking the next morning. In addition, suvorexant decreased protein catabolism and urinary excretion of 3-methylhistidine, but suvorexant did not affect overall energy expenditure during sleep. The orexin system may affect fat oxidation during sleep independent of its roles in sleep regulation in humans.

Free Research Field

睡眠、エネルギー代謝

Academic Significance and Societal Importance of the Research Achievements

本研究の学術的意義は、ヒトの睡眠時エネルギー代謝におけるオレキシン系の役割を一部解明した点にある。特に、スボレキサント投与により脂肪酸化が増大し、タンパク質異化が抑制されることを示した。また、TCAサイクルの中間代謝産物やアミノ酸代謝の変化を尿メタボローム分析で明らかにし、睡眠中の代謝変動にオレキシンが関与していることが示唆された。この知見は、睡眠とエネルギー代謝の調節機構の理解を深化させ、将来的にはオレキシン受容体拮抗薬の応用範囲を拡大する可能性がある。社会的意義としては、睡眠障害に対する治療戦略のみならず、エネルギー代謝の改善を通じて生活習慣病の予防や治療の可能性を広げることが期待される。