Insulin-like growth factor-1 coordinately induces the expression of fatty acid and cholesterol biosynthetic genes in murine C2C12 myoblasts

Background: 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. Results: 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. Conclusion: 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.