Weljie Aalim M, Meerlo Peter, Goel Namni, Sengupta Arjun, Kayser Matthew S, Abel Ted, Birnbaum Morris J, Dinges David F, Sehgal Amita
Department of Pharmacology,
Center for Behavior and Neurosciences, University of Groningen, 9747 AG Groningen, The Netherlands.
Proc Natl Acad Sci U S A. 2015 Feb 24;112(8):2569-74. doi: 10.1073/pnas.1417432112. Epub 2015 Feb 9.
Sleep is an essential biological process that is thought to have a critical role in metabolic regulation. In humans, reduced sleep duration has been associated with risk for metabolic disorders, including weight gain, diabetes, obesity, and cardiovascular disease. However, our understanding of the molecular mechanisms underlying effects of sleep loss is only in its nascent stages. In this study we used rat and human models to simulate modern-day conditions of restricted sleep and addressed cross-species consequences via comprehensive metabolite profiling. Serum from sleep-restricted rats was analyzed using polar and nonpolar methods in two independent datasets (n = 10 per study, 3,380 measured features, 407 identified). A total of 38 features were changed across independent experiments, with the majority classified as lipids (18 from 28 identified). In a parallel human study, 92 metabolites were identified as potentially significant, with the majority also classified as lipids (32 of 37 identified). Intriguingly, two metabolites, oxalic acid and diacylglycerol 36:3, were robustly and quantitatively reduced in both species following sleep restriction, and recovered to near baseline levels after sleep restriction (P < 0.05, false-discovery rate < 0.2). Elevated phospholipids were also noted after sleep restriction in both species, as well as metabolites associated with an oxidizing environment. In addition, polar metabolites reflective of neurotransmitters, vitamin B3, and gut metabolism were elevated in sleep-restricted humans. These results are consistent with induction of peroxisome proliferator-activated receptors and disruptions of the circadian clock. The findings provide a potential link between known pathologies of reduced sleep duration and metabolic dysfunction, and potential biomarkers for sleep loss.
睡眠是一种基本的生物过程，被认为在代谢调节中起关键作用。在人类中，睡眠时间减少与代谢紊乱风险相关，包括体重增加、糖尿病、肥胖症和心血管疾病。然而，我们对睡眠不足影响的分子机制的理解仍处于起步阶段。在本研究中，我们使用大鼠和人类模型来模拟现代睡眠受限的情况，并通过全面的代谢物谱分析来探讨跨物种的后果。在两个独立的数据集中，使用极性和非极性方法分析了睡眠受限大鼠的血清（每项研究n = 10，测量了3380个特征，鉴定出407种）。在独立实验中，共有38个特征发生了变化，其中大多数被归类为脂质（28种已鉴定的脂质中有18种）。在一项平行的人类研究中，92种代谢物被鉴定为可能具有显著性，其中大多数也被归类为脂质（37种已鉴定的脂质中有32种）。有趣的是，两种代谢物，草酸和二酰基甘油36:3，在睡眠受限后在两个物种中均显著且定量地减少，并在睡眠恢复后恢复到接近基线水平（P < 0.05，错误发现率 < 0.2）。在两个物种睡眠受限后还注意到磷脂升高，以及与氧化环境相关的代谢物。此外，反映神经递质、维生素B3和肠道代谢的极性代谢物在睡眠受限的人类中升高。这些结果与过氧化物酶体增殖物激活受体的诱导和生物钟的破坏一致。这些发现提供了已知的睡眠时间减少病理与代谢功能障碍之间的潜在联系，以及睡眠不足的潜在生物标志物。
