Sleep, a mysterious behavior, has recently been recognized as a crucial factor for health and longevity. The daily sleep/wake cycle provides the basis of biorhythms controlling whole-body homeostasis and homeodynamics; therefore, disruption of sleep causes several physical and psychological disorders, including cardiovascular disease, obesity, diabetes, cancer, anxiety, depression, and cognitive dysfunction. However, the mechanism linking sleep disturbances and sleep-related disorders remains unknown. Orexin (also known as hypocretin) is a neuropeptide produced in the hypothalamus. Central levels of orexin oscillate with the daily rhythm and peak at the awake phase. Orexin plays a major role in stabilizing the wakefulness state. Orexin deficiency causes sleep/wake-state instability, resulting in narcolepsy. Hyper-activation of the orexin system also causes sleep disturbances, such as insomnia, and hence, suvorexant, an orexin receptor antagonist, has been clinically used to treat insomnia. Importantly, central actions of orexin regulate motivated behaviors, stress response, and energy/glucose metabolism by coordinating the central-autonomic nervous systems and endocrine systems. These multiple actions of orexin maintain survival. However, it remains unknown whether chronopharmacological interventions targeting the orexin system ameliorate sleep-related disorders as well as sleep in humans. To understand the significance of adequate orexin action for prevention of these disorders, this review summarizes the physiological functions of daily orexin action and pathological implications of its mistimed or reduced action in sleep disturbances and sleep-related disorders (lifestyle-related physical and neurological disorders in particular). Timed administration of drugs targeting the orexin system may prevent lifestyle-related diseases by improving the quality of life in patients with sleep disturbances.

睡眠是一种神秘的行为，最近被认为是健康和长寿的关键因素。每天的睡眠/唤醒周期为控制全身稳态和体内动力学的生物节律提供了基础；因此，睡眠中断会导致多种生理和心理疾病，包括心血管疾病，肥胖，糖尿病，癌症，焦虑症，抑郁症和认知功能障碍。然而，将睡眠障碍和睡眠相关疾病联系起来的机制仍然未知。食欲素（也称为降钙素）是在下丘脑中产生的一种神经肽。食欲素的中央水平随每日节律而振荡，并在清醒阶段达到高峰。食欲素在稳定觉醒状态中起主要作用。食欲素缺乏会引起睡眠/苏醒状态的不稳定性，从而导致发作性睡病。食欲素系统的过度激活还引起睡眠障碍，例如失眠，因此，食欲素（食欲素受体拮抗剂）已被临床用于治疗失眠。重要的是，食欲素的中枢作用通过协调中枢神经系统和内分泌系统来调节动机行为，应激反应和能量/葡萄糖代谢。食欲素的这些多种作用维持生存。然而，针对食欲素系统的时序药理学干预措施能否改善与睡眠有关的疾病以及人类的睡眠，仍然是未知的。要了解适当的食欲素行动对预防这些疾病的重要性，这篇综述总结了日常食欲素作用的生理功能及其在睡眠障碍和与睡眠有关的疾病（特别是与生活方式有关的身体和神经疾病）中误时或减少作用的病理意义。定时服用针对食欲素系统的药物可以通过改善睡眠障碍患者的生活质量来预防与生活方式有关的疾病。