DataSheet2_Hepatic gene expression profiles during fed–fasted–refed state in mice.XLSX

Background: Regulation of nutrient status during fasting and refeeding plays an important role in maintaining metabolic homeostasis in the liver. Thus, we investigated the impact of the physiological Fed–Fast–Refed cycle on hepatic gene expression in nutrient-sensitive mice.
Methods: We performed transcriptomic analysis of liver samples in fed, fasted and refed groups of mice. Through mRNA-sequencing (RNA-Seq) and miRNA-Seq, we compared fasted and fed states (fasted versus fed cohort) as well as refed and fasted states (refed versus fasted cohort) to detect dynamic alterations of hepatic mRNA–miRNA expression during the fed–fasted–refed cycle.
Results: We found dozens of dysregulated mRNAs–miRNAs in the transition from fed to fasted and from fasted to refed states. Gene set enrichment analysis showed that gene expression of the two cohorts shared common pathways of regulation, especially for lipid and protein metabolism. We identified eight significant mRNA and three miRNA clusters that were up–downregulated or down–upregulated during the Fed–Fast–Refed cycle. A protein–protein interaction network of dysregulated mRNAs was constructed and clustered into 22 key modules. The regulation between miRNAs and target mRNAs was presented in a network. Up to 42 miRNA–mRNA-pathway pairs were identified to be involved in metabolism. In lipid metabolism, there were significant correlations between mmu-miR-296-5p and Cyp2u1 and between mmu-miR-novel-chr19_16777 and Acsl3.
Conclusion: Collectively, our data provide a valuable resource for the molecular characterization of the physiological Fed–Fast–Refed cycle in the liver.

研究背景：禁食与复食过程中的营养状态调控，对维持肝脏代谢稳态具有重要作用。为此，本研究针对营养敏感型小鼠，探讨生理状态下的进食-禁食-复食周期对肝脏基因表达的影响。
研究方法：对小鼠进食组、禁食组与复食组的肝脏样本开展转录组分析。通过mRNA测序（RNA-Seq）与miRNA测序，分别对比禁食组与进食组（禁食vs进食队列）、复食组与禁食组（复食vs禁食队列）的转录组数据，以检测进食-禁食-复食周期中肝脏mRNA与miRNA表达的动态变化。
研究结果：在进食向禁食、禁食向复食的状态转换过程中，本研究发现了数十个失调的mRNA与miRNA。基因集富集分析显示，两个队列的基因表达共享共同的调控通路，尤其在脂质与蛋白质代谢方面。本研究鉴定出8个显著的mRNA簇与3个miRNA簇，它们在进食-禁食-复食周期中呈现先上调后下调或先下调后上调的表达模式。构建了失调mRNA的蛋白质相互作用网络，并将其划分为22个关键模块。同时构建了miRNA与靶mRNA的调控网络。最终鉴定出42个参与代谢过程的miRNA-mRNA-通路对。在脂质代谢通路中，mmu-miR-296-5p与Cyp2u1、mmu-miR-novel-chr19_16777与Acsl3分别存在显著的表达相关性。
研究结论：综上，本研究数据为肝脏生理状态下进食-禁食-复食周期的分子特征解析提供了宝贵的研究资源。