Laboratory of Biochemistry, Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan.
Obes Res Clin Pract. 2013 Jul-Aug;7(4):e251-7. doi: 10.1016/j.orcp.2013.01.005.
Orexins are hypothalamic neuropeptides, which play important roles in the regulation and maintenance of sleep/wakefulness states and energy homeostasis. To evaluate whether alterations in orexin system is associated with the sleep/wakefulness abnormalities observed in obesity, we examined the mRNA expression of prepro-orexin, orexin receptor type 1 (orexin 1r), and orexin receptor type 2 (oxexin 2r) in the hypothalamus in mice fed with a normal diet (ND) and high-fat diet (HFD)-induced obese mice. We also compared their relationships with sleep/wakefulness. Twenty-four, 4-week-old, male C57BL/6J mice were divided randomly into three groups, which received the following: (1) ND for 17 weeks; (2) HFD for 17 weeks; and (3) ND for 7 weeks and HFD for a further 10 weeks. The body weights of mice fed the HFD for 10-17 weeks were 112-150% of the average body weight of the ND group. The daily amount of non-rapid eye movement (NREM) sleep increased significantly in HFD-fed mice. These changes were accompanied by increases in the number but decreases in the duration of each NREM sleep episode. In addition, brief awakenings (<20 s epoch) during NREM sleep was nearly 2-fold more frequent. The mRNA level of prepro-orexin in the hypothalamus was significantly reduced in HFD-induced obese mice, whereas the levels of orexin 1r and orexin 2r were unaffected. The daily amount of NREM sleep was negatively correlated with the hypothalamic prepro-orexin mRNA level, so these results suggest that the increased NREM sleep levels in HFD-induced obese mice are attributable to impaired orexin activity.
食欲素是下丘脑神经肽，在调节和维持睡眠/觉醒状态和能量平衡方面发挥重要作用。为了评估食欲素系统的改变是否与肥胖症中观察到的睡眠/觉醒异常有关，我们检查了正常饮食（ND）和高脂肪饮食（HFD）诱导肥胖小鼠下丘脑前食欲素、食欲素受体 1（orexin 1r）和食欲素受体 2（orexin 2r）的 mRNA 表达。我们还比较了它们与睡眠/觉醒的关系。24 只 4 周龄雄性 C57BL/6J 小鼠随机分为三组，分别接受以下处理：（1）ND 喂养 17 周；（2）HFD 喂养 17 周；（3）ND 喂养 7 周，然后 HFD 喂养 10 周。10-17 周 HFD 喂养的小鼠体重增加到 ND 组平均体重的 112-150%。HFD 喂养的小鼠非快速眼动（NREM）睡眠时间的日量显著增加。这些变化伴随着每个 NREM 睡眠期的次数增加但持续时间减少。此外，NREM 睡眠期间的短暂觉醒（<20 秒 epoch）的频率几乎增加了 2 倍。下丘脑前食欲素 mRNA 水平在 HFD 诱导的肥胖小鼠中显著降低，而 orexin 1r 和 orexin 2r 水平不受影响。NREM 睡眠时间的日量与下丘脑前食欲素 mRNA 水平呈负相关，因此这些结果表明 HFD 诱导肥胖小鼠的 NREM 睡眠水平增加归因于食欲素活性受损。
