摘要：SummaryThe insulin responsive Akt and FoxO1 signaling axis is a key regulator of the hepatic transcriptional response to nutrient intake. Here, we used global run-on sequencing (GRO-seq) to measure the nascent transcriptional response to fasting and refeeding as well as define the specific role of hepatic Akt and FoxO1 signaling in mediating this response. We identified 599 feeding-regulated transcripts, as well as over 6,000 eRNAs, and mapped their dependency on Akt and FoxO1 signaling. Further, we identified several feeding-regulated lncRNAs, including the lncRNAGm11967, whose expression was dependent upon the liver Akt-FoxO1 axis. RestoringGm11967expression in mice lacking liver Akt improved insulin sensitivity and induced glucokinase protein expression, indicating that Akt-dependent control ofGm11967contributes to the translational control of glucokinase. More broadly, we have generated a unique genome-wide dataset that defines the feeding and Akt/FoxO1-dependent transcriptional changes in response to nutrient availability.Graphical abstractDisplay OmittedHighlights•The hepatic transcriptional response to nutrients was determined by GRO-seq•The role of Akt/FoxO1 on feeding-dependent nascent transcripts was characterized•The lncRNA,Gm11967, was identified as a translational regulator of glucokinasePhysiology; Molecular physiology; Omics; Transcriptomics
