Mavanji Vijayakumar, Perez-Leighton Claudio E, Kotz Catherine M, Billington Charles J, Parthasarathy Sairam, Sinton Christopher M, Teske Jennifer A
Minneapolis VA Health Care System, Minneapolis, MN.
Center for Integrative Medicine and Innovative Science, Universidad Andres Bello, Santiago, Chile.
Sleep. 2015 Sep 1;38(9):1361-70. doi: 10.5665/sleep.4970.
The ventrolateral preoptic area (VLPO) and the orexin/hypocretin neuronal system are key regulators of sleep onset, transitions between vigilance states, and energy homeostasis. Reciprocal projections exist between the VLPO and orexin/hypocretin neurons. Although the importance of the VLPO to sleep regulation is clear, it is unknown whether VLPO neurons are involved in energy balance. The purpose of these studies was to determine if the VLPO is a site of action for orexin-A, and which orexin receptor subtype(s) would mediate these effects of orexin-A. We hypothesized that orexin-A in the VLPO modulates behaviors (sleep and wakefulness, feeding, spontaneous physical activity [SPA]) to increase energy expenditure.
Sleep, wakefulness, SPA, feeding, and energy expenditure were determined after orexin-A microinjection in the VLPO of male Sprague-Dawley rats with unilateral cannulae targeting the VLPO. We also tested whether pretreatment with a dual orexin receptor antagonist (DORA, TCS-1102) or an OX2R antagonist (JNJ-10397049) blocked the effects of orexin-A on the sleep/wake cycle or SPA, respectively.
Orexin-A injected into the VLPO significantly increased wakefulness, SPA, and energy expenditure (SPA-induced and total) and reduced NREM sleep and REM sleep with no effect on food intake. Pretreatment with DORA blocked the increase in wakefulness and the reduction in NREM sleep elicited by orexin-A, and the OX2R antagonist reduced SPA stimulated by orexin-A.
These data show the ventrolateral preoptic area is a site of action for orexin-A, which may promote negative energy balance by modulating sleep/wakefulness and stimulating spontaneous physical activity and energy expenditure.
腹外侧视前区（VLPO）和食欲素/下丘脑泌素神经元系统是睡眠起始、警觉状态转换及能量平衡的关键调节因子。VLPO与食欲素/下丘脑泌素神经元之间存在相互投射。尽管VLPO对睡眠调节的重要性已明确，但VLPO神经元是否参与能量平衡尚不清楚。这些研究的目的是确定VLPO是否为食欲素-A的作用位点，以及哪种食欲素受体亚型介导食欲素-A的这些作用。我们假设VLPO中的食欲素-A调节行为（睡眠和觉醒、进食、自发身体活动[SPA]）以增加能量消耗。
在单侧插管靶向VLPO的雄性Sprague-Dawley大鼠的VLPO中微量注射食欲素-A后，测定睡眠、觉醒、SPA、进食和能量消耗。我们还测试了用双重食欲素受体拮抗剂（DORA，TCS-1102）或OX2R拮抗剂（JNJ-10397049）预处理是否分别阻断了食欲素-A对睡眠/觉醒周期或SPA的影响。
向VLPO注射食欲素-A显著增加觉醒、SPA和能量消耗（由SPA诱导的和总的），减少非快速眼动睡眠和快速眼动睡眠，对食物摄入无影响。用DORA预处理可阻断食欲素-A引起的觉醒增加和非快速眼动睡眠减少，OX2R拮抗剂可减少食欲素-A刺激的SPA。
这些数据表明腹外侧视前区是食欲素-A的作用位点，食欲素-A可能通过调节睡眠/觉醒和刺激自发身体活动及能量消耗来促进负能量平衡。
