Functional roles of orexin in obstructive sleep apnea: From clinical observation to mechanistic insights

Obstructive sleep apnea is the most common sleep-related breathing disorder. Repetitive episodes of the obstructive respiratory events lead to arousal, sleep fragmentation, and excessive daytime sleepiness. Orexin, also known as hypocretin, is one of the most important neurotransmitters responsible for sleep and arousal regulation. Deficiency of orexin has been shown to be involved in the pathogenesis of narcolepsy, which shares cardinal symptoms of sleep apnea and excessive daytime sleep with obstructive sleep apnea. However, the relationship between orexin and obstructive sleep apnea is not well defined. In this review, we summarize the current evidence, from in vitro, in vivo, and clinical data, regarding the association between orexin and obstructive sleep apnea. The effects of orexin on sleep apnea, as well as how the consequences of obstructive sleep apnea affect the orexin system function are also discussed. Additionally, the contrary findings are also included and discussed.