Interorgan Coordination of the Murine Adaptive Response to Fasting

摘要: Starvation elicits a complex adaptive response in an organism. No information on transcriptional regulation of metabolic adaptations is available. We, therefore, studied the gene expression profiles brain, small intestine, kidney, liver, and skeletal muscle mice that were subjected to 0-72 h fasting. Functional-category enrichment, text mining, network analyses employed scrutinize overall adaptation, aiming identify responsive pathways, processes, networks, their regulation. The observed transcriptomics did not follow accepted "carbohydrate-lipid-protein" succession expenditure energy substrates. Instead, these processes activated simultaneously different organs during entire period. most prominent changes occurred lipid steroid metabolism, especially liver kidney. They accompanied by suppression immune cell turnover, particularly increased proteolysis muscle. brain was extremely well protected from sequels starvation. 60% identified overconnected transcription factors organ-specific, 6% common for 4 organs, with nuclear receptors as protagonists, accounting almost 40% all regulators PPARα, HNF4α, GCRα, AR (androgen receptor), SREBP1 -2, FOXOs, EGR1, c-JUN, c-MYC, SP1, YY1, ETS1. Our data strongly suggest control metabolism four metabolically active exerted are nutrient signals serves, at least partly, prevent irreversible damage.