Roles of orexin in energy metabolism during sleep in humans

Tsukuba, Japan—Orexin, named after its role in feeding regulation, is a potent endogenous sleep/wake state regulator and is expected to play an essential role in controlling the cross-talk mechanism between sleep/wake and energy metabolism. In 2014, suvorexant, an orexin receptor antagonist, was approved for treating insomnia, allowing for the physiological functions of orexin to be studied 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. 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.

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This research was supported by the World Premier International Research Center Initiative (WPI), AMED under Grant Number JP21zf0127005 and the Japan Society for Promotion of Science KAKENHI (Grant-in-Aid for Early-Career Scientists [JP21K17657]).

_{Original Paper}

Title of original paper:
Orexin receptor antagonist increases fat oxidation and suppresses protein catabolism during sleep in humans

Journal:
iScience

DOI:
10.1016/j.isci.2024.110212

_{Correspondence}

Professor Emeritus TOKUYAMA, Kumpei 
International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba

_{Related Link}

International Institute for Integrative Sleep Medicine (WPI-IIIS)

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About International Institute for Integrative Sleep Medicine (IIIS), University of Tsukuba
World-class institute for sleep medicine, aiming to solve the mechanism of sleep/wakefulness by conducting basic to translational research
The mission of IIIS is to be a multidisciplinary, international hub for the research to elucidate the function of sleep and the fundamental mechanisms of sleep/wake regulation, to elucidate molecular pathogenesis of sleep disorders and related diseases, to develop preventive measures, diagnostic methods, and treatments for sleep.