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

Insung Park1, Rikako Yoshitake2, Kazuki Kioka2

  • 1International Institute for Integrative Sleep Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.

Iscience
|July 12, 2024
PubMed

Insights

Suvorexant, an orexin receptor antagonist, altered sleep stages and fat metabolism in healthy men. It increased fat oxidation during sleep and reduced protein breakdown, suggesting orexin

Area of Science:

  • Neuroscience
  • Metabolic research
  • Sleep science

Background:

  • Orexin signaling regulates wakefulness and is implicated in energy metabolism in rodents.
  • The role of orexin in human energy metabolism, particularly during sleep and post-awakening, is not well understood.

Purpose of the Study:

  • To investigate the effects of suvorexant, an orexin receptor antagonist, on energy metabolism during sleep and shortly after awakening in healthy men.
  • To explore the potential role of the orexin system in regulating human energy expenditure and substrate oxidation.

Main Methods:

  • A randomized, double-blind, placebo-controlled, crossover study involving 14 healthy male participants.
  • Administration of suvorexant (20 mg) or placebo, with assessment of sleep stages (REM, NREM) and energy expenditure.
  • Measurement of substrate oxidation (fat and protein) during sleep and wakefulness after sleep onset (WASO).

Main Results:

  • Suvorexant increased REM sleep and decreased NREM stage 1 sleep.
  • Energy expenditure during WASO was elevated with placebo but not suvorexant, suggesting orexin's role in wake-related energy expenditure.
  • Fat oxidation during sleep increased with suvorexant and persisted post-awakening; protein catabolism decreased, but overall energy expenditure remained unchanged.

Conclusions:

  • The orexin system influences energy expenditure during wakefulness after sleep onset in humans.
  • Suvorexant administration impacts fat oxidation during sleep, potentially independent of its sleep-regulating functions.
  • These findings suggest a distinct role for the orexin system in modulating human metabolic processes beyond sleep control.
Keywords:
Health sciencesHuman metabolismPhysiology

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