A study of suvorexant, an orexin receptor antagonist, found that it prolongs REM sleep, promotes fat burning, and reduces protein catabolism, suggesting novel clinical applications beyond sleep regulation.
New research highlights the dual action of suvorexant on sleep and metabolism, showing that it enhances fat burning and reduces protein breakdown during sleep, suggesting new clinical applications for orexin antagonists in the treatment of insomnia.
Orexin, named for its role in feeding regulation, is a potent endogenous regulator of sleep and wakefulness and is believed to play a crucial role in the interplay between sleep/wake cycles and energy metabolism. In 2014, the orexin receptor antagonist suvorexant was approved for the treatment of insomnia, enabling the study of the physiological functions of orexin in humans.
However, the role of the orexin system in the regulation of energy metabolism remains unclear in humans. In this randomized, double-blind, placebo-controlled, crossover study, investigators evaluated the impact of suvorexant (20 mg) on energy metabolism during sleep and the subsequent wakefulness period in 14 healthy men. Total sleep time did not change significantly following suvorexant treatment; however, there was an increase in rapid eye movement (REM) sleep and a decrease in non-REM stage 1 sleep.
EEG recording during indirect calorimetry using a whole-room metabolic chamber. Credit: University of Tsukuba
Effects of Suvorexant on metabolism
Suvorexant specifically promoted fat burning during sleep, with the effect lasting up to the first hour after waking in the morning. In addition, suvorexant reduced protein catabolism, although it did not affect total energy expenditure during sleep.
These results suggest that the orexin system influences fat oxidation and protein catabolism independently of its role in sleep/wake control, suggesting another potential clinical use of orexin receptor antagonists in the long term. The findings of this study shed light on the choice of hypnotic agents for patients with insomnia.
Reference: “Orexin receptor antagonist enhances fat oxidation and suppresses protein catabolism during sleep in humans” by Insung Park, Rikako Yoshitake, Kazuki Kioka, Asuka Ishihara, Katsuhiko Yajima, Fusae Kawana, Toshio Kokubo, Ichiyo Matsuzaki, Takashi Kanbayashi, Masashi Yanagisawa, and Kumpei Tokuyama, June 6, 2024, iScience.
DOI: 10.1016/j.isci.2024.110212