Transcriptional profiling of the response to starvation and fattening reveals differential regulation of autophagy genes in mammals

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 analyze 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 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 m..., ,