Tissue-Specific Dissociation of Diurnal Transcriptome Rhythms During Sleep Restriction in Mice
Tissue-Specific Dissociation of Diurnal Transcriptome Rhythms During Sleep Restriction in Mice
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DOI：
10.1093/sleep/zsx068
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发表时间：
2017-06-01
期刊：
影响因子：
5.6
通讯作者：
Oster, Henrik
中科院分区：
文献类型：
--
作者：
Husse, Jana;Kiehn, Jana-Thabea;Oster, Henrik
研究目的：睡眠时间缩短或不定时影响代谢稳态，这可能部分由内源性生物钟失调介导。在这项研究中，我们评估了睡眠中断代谢失调的贡献，通过分析昼夜转录组调节代谢组织的小鼠进行了睡眠限制（SR）paradigm.Methods：雄性小鼠进行了2 × 5天的SR与强制唤醒在第一个6小时的光相。SR和对照小鼠在一天中的不同时间点处死，并对来自中基底下丘脑（MBH）、肝脏和附睾白色脂肪组织（eWAT）的RNA制备物进行全基因组微阵列杂交。转录节律与行为和生理参数（如睡眠、体温和食物摄入）的变化相关。节奏检测与CircWave和转录配置文件进行了比较，通过双向方差分析和t-检验Benjamini-Hochberg corrections.Results：时钟基因的节奏钝化在所有组织中，而转录调控与时钟基因的表达，睡眠模式，或食物摄入量在组织特异性的方式。时钟基因表达与MBH中的细胞凋亡途径和肝脏中的肿瘤坏死因子α信号传导相关。食物摄入相关的基因包括纤毛运动基因的MBH和脂质代谢相关的成绩单在liver.Conclusions：在小鼠中，反复SR深刻地改变行为和分子昼夜节律，破坏必不可少的信号通路MBH，肝脏，和eWAT，这可能是睡眠限制的人，如轮班工人的代谢和认知障碍的基础。
Study objectives: Shortened or mistimed sleep affects metabolic homeostasis, which may in part be mediated by dysregulation of endogenous circadian clocks. In this study, we assessed the contribution of sleep disruption to metabolic dysregulation by analysing diurnal transcriptome regulation in metabolic tissues of mice subjected to a sleep restriction (SR) paradigm.Methods: Male mice were subjected to 2 x 5 days of SR with enforced waking during the first 6 hours of the light phase. SR and control mice were sacrificed at different time points of the day and RNA preparations from the mediobasal hypothalamus (MBH), liver, and epididymal white adipose tissue (eWAT) were subjected to whole-genome microarray hybridization. Transcriptional rhythms were associated with changes in behavioral and physiological parameters such as sleep, body temperature, and food intake. Rhythm detection was performed with CircWave and transcription profiles were compared by 2-way analysis of variance and t-tests with Benjamini-Hochberg corrections.Results: Clock gene rhythms were blunted in all tissues, while transcriptome regulation was associated with either clock gene expression, sleep patterns, or food intake in a tissue-specific manner. Clock gene expression was associated with apoptosis pathways in the MBH and with tumor necrosis factor alpha signalling in liver. Food intake-associated genes included cilium movement genes in the MBH and lipid metabolism-associated transcripts in liver.Conclusions: In mice, repeated SR profoundly alters behavioral and molecular diurnal rhythms, disrupting essential signalling pathways in MBH, liver, and eWAT, which may underlie the metabolic and cognitive disturbances observed in sleep-restricted humans such as shift workers.