A study on suvorexant, an orexin receptor antagonist, revealed its role in increasing REM sleep, promoting fat oxidation, and reducing protein catabolism, suggesting new clinical uses beyond sleep regulation.
New research highlights the dual effects of suvorexant on sleep and metabolism, showing it enhances fat oxidation and reduces protein breakdown during sleep, suggesting new clinical uses for orexin antagonists in treating insomnia.
Orexin, named for its role in feeding regulation, is a powerful endogenous regulator of sleep and wakefulness and is believed to play a critical role in the interaction 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 orexin’s physiological functions in humans.
However, the role of orexin system in the regulation of energy metabolism remains unclear in humans. In this randomized, double-blind, placebo-controlled, crossover study, the researchers evaluated the impact of suvorexant (20 mg) on energy metabolism during sleep and the subsequent wake-up period in 14 healthy men. The 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 sleep stage 1.
EEG record during indirect calorimetry using a whole room metabolic chamber. Credit: University of Tsukuba
Effects of Suvorexant on Metabolism
Notably, suvorexant promoted fat oxidation during sleep, with the effect persisting up to the first hour after waking up in the morning. In addition, suvorexant decreased protein catabolism, although it did not impact overall energy expenditure during sleep.
These results suggest that the orexin system affects fat oxidation and protein catabolism independent of its roles in sleep/wake control, indicating another potential clinical use of orexin receptor antagonists in the long term. The findings of this study shed light on choosing hypnotic agents for patients with insomnia.
Reference: “Orexin receptor antagonist increases 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, 6 June 2024, iScience.
DOI: 10.1016/j.isci.2024.110212
