Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel Aviv University, 6997801 Tel Aviv, Israel.
Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, 6997801 Tel Aviv, Israel.
Proc Biol Sci. 2023 Mar 29;290(1995):20230407. doi: 10.1098/rspb.2023.0407.
Nutrient deprivation (starvation) induced by fasting and hypercaloric regimens are stress factors that can influence cell and tissue homeostasis in mammals. One of the key cellular responses to changes in nutrient availability is the cell survival pathway autophagy. While there has been much research into the protein networks regulating autophagy, less is known about the gene expression networks involved in this fundamental process. Here, we applied a network algorithm designed to analyse omics datasets, to identify sub-networks that are enriched for induced genes in response to starvation. This enabled us to identify two prominent active modules, one composed of key stress-induced transcription factors, including members of the Jun, Fos and ATF families, and the other comprising autophagosome sub-network genes, including ULK1. The results were validated in the brain, liver and muscle of fasting mice. Moreover, differential expression analysis of autophagy genes in the brain, liver and muscle of high-fat diet-exposed mice showed significant suppression of GABARAPL1 in the liver. Finally, our data provide a resource that may facilitate the future identification of regulators of autophagy.
禁食和高卡路里疗法引起的营养缺乏（饥饿）是应激因素，可影响哺乳动物的细胞和组织动态平衡。细胞对营养供应变化的关键反应之一是自噬细胞存活途径。虽然已经有很多关于调节自噬的蛋白质网络的研究，但对于涉及这一基本过程的基因表达网络知之甚少。在这里，我们应用了一种专门用于分析组学数据集的网络算法，来识别响应饥饿而富集诱导基因的子网络。这使我们能够识别出两个突出的活跃模块，一个由关键应激诱导的转录因子组成，包括 Jun、Fos 和 ATF 家族的成员，另一个由自噬体子网基因组成，包括 ULK1。在禁食小鼠的大脑、肝脏和肌肉中验证了这些结果。此外，对高脂肪饮食暴露小鼠大脑、肝脏和肌肉中的自噬基因进行差异表达分析显示，肝脏中 GABARAPL1 的表达显著受到抑制。最后，我们的数据提供了一个资源，可能有助于未来鉴定自噬的调节剂。
