Department of Child, Adolescent and Women's Health, School of Public Health, Capital Medical University, Beijing, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, China.
Department of Child, Adolescent and Women's Health, School of Public Health, Capital Medical University, Beijing, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, China.
J Proteomics. 2021 Aug 15;245:104290. doi: 10.1016/j.jprot.2021.104290. Epub 2021 Jun 2.
Sleep deprivation (SD) has been linked to impaired mental and physical health, obesity, and various diseases. However, the molecular mechanism underlying the effects of SD in the liver is still unclear. To investigate the metabolome and proteome alterations in the liver, an in vivo model of SD was established based on automated random motion platform techniques by applying a strategy of 10 consecutive days of 20 h of sleep deprivation +4 h of resting. The liver's altered metabolites and proteins were detected by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and data analyses were performed with MetaboAnalyst 5.0. This study found 15 differential metabolites, including 12 upregulated- metabolites and 3 downregulated- metabolites. A total of 493 proteins were differentially regulated, including 377 upregulated- proteins and 116 downregulated- proteins. The glutathione metabolism, fructose and mannose metabolism, and pyruvate metabolism pathways had significant effects on the sleep-deprived mouse livers. These three active pathways cause energy metabolism disorder and may induce obesity. In conclusion, this study demonstrates that SD could change the metabolism of glucose, and specific fatty acids, amino acids, and critical enzymes in the liver, providing a reference for the health effects of insufficient sleep. SIGNIFICANCE STATEMENT: So far, little is known about the changes in metabolites and proteins in the liver of individuals who suffer from SD. Metabolites and proteins in serum, urine and hypothalamus do not entirely reflect the effects of sleep deprivation on the whole body. In addition, many SD-induced models used the multiplatform water environment method, which causes mice to fall into the water frequently. Under this condition, the physical exertion of mice is extremely high, and it is not suitable for long-term sleep deprivation. The SD induction process has caused some influence on the model. Finally, few studies have elucidated the imbalance of energy metabolism caused by SD to induce obesity from the molecular mechanism. This study used a rotary table deprivation apparatus to trigger SD. This method will not cause excessive consumption and stimulation of mice. Furthermore, this study analyzed the metabolic and proteomic changes in the liver and enriched the range and means of metabolic and proteomic changes in sleep deprived mice. Finally, this research provides reference for elucidating the molecular mechanism of sleep deprivation causing energy metabolism disorders in the liver of mice.
睡眠剥夺（SD）与精神和身体健康受损、肥胖和各种疾病有关。然而，SD 对肝脏影响的分子机制尚不清楚。为了研究肝脏的代谢组和蛋白质组变化，本研究基于自动化随机运动平台技术，通过应用连续 10 天 20 小时睡眠剥夺+4 小时休息的策略，建立了 SD 的体内模型。采用液相色谱-串联质谱（LC-MS/MS）检测肝脏中改变的代谢物和蛋白质，并用 MetaboAnalyst 5.0 进行数据分析。本研究发现了 15 种差异代谢物，包括 12 种上调代谢物和 3 种下调代谢物。共有 493 种蛋白质差异调节，包括 377 种上调蛋白和 116 种下调蛋白。谷胱甘肽代谢、果糖和甘露糖代谢以及丙酮酸代谢途径对睡眠剥夺小鼠肝脏有显著影响。这三个活跃的途径导致能量代谢紊乱，可能会导致肥胖。总之，本研究表明 SD 可改变肝脏中葡萄糖和特定脂肪酸、氨基酸和关键酶的代谢，为睡眠不足对健康的影响提供了参考。
意义陈述：到目前为止，人们对遭受 SD 的个体肝脏中代谢物和蛋白质的变化知之甚少。血清、尿液和下丘脑的代谢物和蛋白质并不能完全反映睡眠剥夺对全身的影响。此外，许多 SD 诱导模型使用多平台水环境方法，导致老鼠经常掉入水中。在这种情况下，老鼠的体力消耗极高，不适合长期睡眠剥夺。SD 诱导过程对模型产生了一些影响。最后，很少有研究从分子机制上阐明 SD 引起的能量代谢失衡导致肥胖。本研究使用转台剥夺装置来引发 SD。这种方法不会导致老鼠过度消耗和刺激。此外，本研究分析了肝脏的代谢组学和蛋白质组学变化，并丰富了睡眠剥夺小鼠代谢组学和蛋白质组学变化的范围和手段。最后，本研究为阐明 SD 导致小鼠肝脏能量代谢紊乱的分子机制提供了参考。
