The orexin receptor antagonist enhanced fat oxidation and reduced protein catabolism during sleep, in a new study, indicating potential metabolic benefits.


Summary: A new randomized, double-blind, placebo-controlled crossover study has found that suvorexant, an orexin receptor antagonist approved for treating insomnia, promotes fat oxidation and reduces protein catabolism during sleep without significantly changing total sleep time. The study highlights the metabolic effects of the orexin system, suggesting additional clinical benefits of orexin receptor antagonists.

Key Takeaways:

  • Fat Oxidation: Suvorexant was shown to increase fat oxidation during sleep, with the effect continuing into the first hour after waking up.
  • Protein Catabolism: The drug also decreased protein catabolism, indicating a potential protective effect on muscle protein during sleep.
  • Metabolic Benefits: These findings suggest that orexin receptor antagonists like suvorexant could have metabolic benefits beyond their primary use for treating insomnia.

A new study has found that suvorexant, an orexin receptor antagonist used to treat insomnia, promotes fat oxidation during sleep and reduces protein catabolism, suggesting potential metabolic benefits.

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. 

Evaluating Suvorexant’s Impact on Sleep and Metabolism

In a new randomized, double-blind, placebo-controlled, crossover study, 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, published in iScience, shed light on choosing hypnotic agents for patients with insomnia.

Photo caption: EEG record during indirect calorimetry using a whole room metabolic chamber. 

Photo credit: University of Tsukuba