Sleep profile during fasting in PPAR-alpha knockout mice
Sleep profile during fasting in PPAR-alpha knockout mice
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DOI：
10.1016/j.physbeh.2019.112760
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发表时间：
2020-02-01
影响因子：
2.9
通讯作者：
Sei, Hiroyoshi
中科院分区：
文献类型：
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作者：
Kondo, Yoshitsugu;Chikahisa, Sachiko;Sei, Hiroyoshi
过氧化物酶体增殖物激活受体α（Peroxisome proliferator-activated receptor alpha，PPARalpha）是核受体家族中的一种转录因子，在调节脂质代谢相关基因表达中起重要作用。过氧化物酶体增殖物激活受体α促进肝脏脂肪酸氧化和酮生成反应禁食。由于已知能量代谢会影响睡眠调节，因此改变PPAR α的操作可能会影响睡眠和其他生理表型。在这项研究中，我们研究的作用，过氧化物酶体增殖物激活受体α在睡眠/觉醒调节使用过氧化物酶体增殖物激活受体α基因敲除（KO）小鼠。在随意进食条件和24小时食物剥夺（FD）下，记录KO小鼠和野生型（WT）对照中的睡眠、体温（BT）、自发活动、动脉压（AP）和心率（HR）。KO和WT小鼠在基础睡眠量、BT、平均AP和HR方面相同，尽管KO小鼠显示出增强的嗜睡（增强的EEG慢波活动）。在对FD的反应中，KO小鼠在黑暗期结束时显示出觉醒和运动活动的大幅下降，而WT小鼠则没有。同样，AP和HR，这是抑制FD，减少KO比WT小鼠。与WT小鼠相比，KO小鼠在FD条件下显示血浆酮体浓度降低，肝脏和大脑中生酮酶基因Hmgcs 2的mRNA表达降低。这些结果表明，过氧化物酶体增殖物激活受体α和/或脂质代谢参与维持清醒和运动活动，在禁食小鼠。
Peroxisome proliferator-activated receptor alpha (PPAR alpha) is a transcription factor that belongs to the nuclear receptor family and plays an important role in regulating gene expression associated with lipid metabolism. PPAR alpha promotes hepatic fatty acid oxidation and ketogenesis in response to fasting. Because energy metabolism is known to affect sleep regulation, manipulations that change PPAR alpha are likely to affect sleep and other physiological phenotypes. In this study, we examined the role of PPAR alpha in sleep/wake regulation using PPAR alpha knockout (KO) mice. Sleep, body temperature (BT), locomotor activity, arterial pressure (AP) and heart rate (HR) were recorded in KO mice and wild-type (WT) controls under ad libitum-fed conditions and 24-hour food deprivation (FD). KO and WT mice were identical in basal sleep amount, BT, mean AP and HR, although KO mice showed enhanced sleepiness (enhanced EEG slow-wave activity). In response to FD, KO mice showed a large drop in wakefulness and locomotor activity at the end of the dark phase, whereas WT mice did not. Similarly, AP and HR, which were suppressed by FD, decreased more in KO than in WT mice. Compared to WT mice, KO mice showed a reduced concentration of plasma ketone bodies and decreased mRNA expression of the ketogenic enzyme gene Hmgcs2 in the liver and brain under FD conditions. These results suggest that PPAR alpha and/or lipid metabolism is involved in the maintenance of wakefulness and locomotor activity during fasting in mice.