Insulin-like growth factor-1 coordinately induces the expression of fatty acid and cholesterol biosynthetic genes in murine C2C12 myoblasts
Center for Molecular Genetics, Department of Pediatrics, School of Medicine, University of California, San Diego, La Jolla CA 92093-0634 USA
BMC Genomics 2008, 9:535 doi:10.1186/1471-2164-9-535Published: 11 November 2008
We present evidence that a major aspect of the mechanism of acute signal transduction regulation by insulin-like growth factor-1 (IGF-1) in cultured murine myoblasts is associated with a broad perturbation of many components of cholesterol and fatty acid biosynthetic pathways.
We have used microarray transcriptional analysis to examine the acute effects of IGF-1 on global patterns of gene expression in C2C12 myoblasts and have identified approximately 157 genes that are up-regulated and 75 genes down-regulated from 2- to 6-fold after treatment with IGF-1. Of the up-regulated genes, 19 genes are associated with cholesterol biosynthesis and 5 genes specify aspects of fatty acid biosynthesis. In addition 10 recognized transcription factors are significantly induced by IGF-1 at 1 hour.
The SREBPs, important regulators of fatty acid and cholesterol biosynthesis, operate via a post-transcriptional route and no significant transcriptional induction was observed in the 4 hr of IGF-1 treatment. Since there are no prior reports of significant and coordinated perturbations of fatty acid and cholesterol biosynthetic pathways with IGF-1 in muscle cells, these findings provide a substantive expansion of our understanding of IGF-1 action and the signal transduction pathways mediated by it, its variants and insulin.