2024-03-29T10:14:59Zhttps://eprints.lib.hokudai.ac.jp/dspace-oai/requestoai:eprints.lib.hokudai.ac.jp:2115/548152022-11-17T02:08:08Zhdl_2115_20048hdl_2115_140Hypothalamic prepro-orexin mRNA level is inversely correlated to the non-rapid eye movement sleep level in high-fat diet-induced obese miceTanno, ShogoTerao, AkiraOkamatsu-Ogura, YukoKimura, KazuhiroObesityHigh-fat dietOrexinNon-rapid eye movement sleep649Orexins 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. (C) 2013 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.ElsevierJournal Articleapplication/pdfhttp://hdl.handle.net/2115/54815https://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/54815/1/Tanno%20Manuscript2.pdf1871-403XObesity Research & Clinical Practice74E251E2572013-07enginfo:pmid/24306152info:doi/10.1016/j.orcp.2013.01.005author