Characterization of transcriptome changes induced in 3T3L1 adipocytes by expression of Adenovirus subtype 5 protein E4-ORF1. Mus musculus

Insulin activation of phosphoinositol 3-kinase (PI3 kinase) regulates metabolism, including the translocation of the Glut4 glucose transporter to plasma membrane and inactivation of FoxO1 transcription factor. Adenoviral protein E4-ORF1 stimulates cellular glucose metabolism by mimicking growth factor activation of PI3 kinase. We have used E4-ORF1 to dissect PI3 kinase-mediated signaling in adipocytes. E4-ORF1 activation of PI3 kinase recapitulates insulin-regulation of FoxO1 but not regulation of Glut4. This uncoupling of PI3 kinase effects occurs despite E4-ORF1 activating PI3 kinase and downstream signaling to levels achieved by insulin. Although, E4-ORF1 does not fully recapitulate insulin’s effects on Glut4, it enhances insulin-stimulated insertion of Glut4-containing vesicles to the plasma membrane independent of Rab10, a key regulator of Glut4 trafficking. E4-ORF1 also stimulates plasma membrane translocation of ubiquitously expressed Glut1 glucose transporter an effect that is likely essential for E4-ORF1 to promote an anabolic metabolism in a broad range of cell types. Overall design: mRNA profiles of wild type and E4-ORF1 stably expressing adipocytes generated by deep sequencing, in triplicate, using Illumina HTDNA sequencing.