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Orexin receptor antagonist increases fat oxidation and suppresses protein catabolism during sleep in humans.

ABSTRACT: Suvorexant is an orexin receptor antagonist that targets the wake-promoting system. Orexin is also known to regulate energy metabolism in rodents, but its role in humans remains largely unknown. Here, we assessed the effect of suvorexant (20 mg) on energy metabolism during sleep and shortly after awakening in a randomized, double-blind, placebo-controlled, crossover study in 14 healthy men. Suvorexant increased rapid eye movement (REM) but decreased nonrapid eye movement (NREM) stage 1. Energy expenditure during wake after sleep onset (WASO) was higher than that during NREM and REM sleep in the placebo but not in the suvorexant trial, suggesting that the increase in energy expenditure during WASO was due to an activation of the orexin system. Fat oxidation during sleep increased, and its effect remained after waking the next morning. Suvorexant decreased protein catabolism but did not affect overall energy expenditure. The orexin system may affect fat oxidation independent of its roles in sleep regulation in humans.

SUBMITTER: Park I

PROVIDER: S-EPMC11238128 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature

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Orexin receptor antagonist increases fat oxidation and suppresses protein catabolism during sleep in humans.

Park Insung I Yoshitake Rikako R Kioka Kazuki K Ishihara Asuka A Yajima Katsuhiko K Kawana Fusae F Kokubo Toshio T Matsuzaki Ichiyo I Kanbayashi Takashi T Yanagisawa Masashi M Tokuyama Kumpei K

iScience 20240606 7

Suvorexant is an orexin receptor antagonist that targets the wake-promoting system. Orexin is also known to regulate energy metabolism in rodents, but its role in humans remains largely unknown. Here, we assessed the effect of suvorexant (20 mg) on energy metabolism during sleep and shortly after awakening in a randomized, double-blind, placebo-controlled, crossover study in 14 healthy men. Suvorexant increased rapid eye movement (REM) but decreased nonrapid eye movement (NREM) stage 1. Energy e ...[more]

PMID: 38993665

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Project description:Study objectivesSuvorexant (MK-4305) is an orexin receptor antagonist being developed for the treatment of insomnia. This report describes the effects of nighttime administration of suvorexant on polysomnography (PSG) sleep parameters in healthy young men.DesignRandomized, double-blind, placebo-controlled, 4-period crossover PSG study, followed by an additional 5(th) period to assess pharmacokinetics.SettingSleep laboratory.ParticipantsHealthy young men between 18 and 45 years of age (22 enrolled, 19 completed).InterventionsPeriods 1-4: suvorexant (10 mg, 50 mg, or 100 mg) or placebo 1 h before nighttime PSG recording. Period 5: suvorexant 10 mg, 50 mg, or 100 mg.Measurements and resultsIn Periods 1-4, overnight sleep parameters were recorded by PSG and next-morning residual effects were assessed by psychomotor performance tests and subjective assessments. Statistically significant sleep-promoting effects were observed with all doses of suvorexant compared to placebo. Suvorexant 50 mg and 100 mg significantly decreased latency to persistent sleep and wake after sleep onset time, and increased sleep efficiency. Suvorexant 10 mg significantly decreased wake after sleep onset time. There were no statistically significant effects of suvorexant on EEG frequency bands including delta (slow wave) activity based on power spectral analysis. Suvorexant was well tolerated. There was no evidence of next-day residual effects for suvorexant 10 mg. Suvorexant 50 mg statistically significantly reduced subjective alertness, and suvorexant 100 mg significantly increased reaction time and reduced subjective alertness. There were no statistically significant effects of any suvorexant dose on digit symbol substitution test performance. In Period 5, plasma samples of suvorexant were collected for pharmacokinetic evaluation. The median T(max) was 3 hours and apparent terminal t(½) was 9-13 hours.ConclusionsIn healthy young men without sleep disorders, suvorexant promoted sleep with some evidence of residual effects at the highest doses.

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Orexin receptor antagonist increases fat oxidation and suppresses protein catabolism during sleep in humans.

Publications

Orexin receptor antagonist increases fat oxidation and suppresses protein catabolism during sleep in humans.

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