ISL1 Regulates PPARgamma Activation and Early Adipogenesis via BMP4-Dependent and -Independent Mechanisms
While adipogenesis is controlled by a cascade of transcription factors, the global gene expression profiles in the early phase of adipogenesis are not well defined. Using microarray analysis of gene expression in 3T3-L1 cells we have identified evidence for the activity of 2568 genes during the early phase of adipocyte differentiation. One of these, ISL1, was of interest since its expression was markedly upregulated at 1 h after initiation of differentiation with a subsequent rapid decline. Overexpression of ISL1 at early times during adipocyte differentiation, but not at later times, was found to profoundly inhibit differentiation. This was accompanied by moderate down-regulation of PPARgamma levels, substantial down-regulation of PPARgamma downstream genes and down-regulation of BMP4 levels in preadipocytes. Readdition of BMP4 overcame the inhibitory effect of ISL1 on PPARgamma but not aP2 expression, a downstream gene of PPARgamma; and BMP4 also partially rescued ISL1 inhibition of adipogenesis, an effect which is additive with rosiglitazone. These results suggest that ISL1 is intimately involved in early regulation of adipogenesis, modulating PPARgamma expression and activity via BMP4-dependent and -independent mechanisms. Our time course gene expression survey sets the stage for further studies to explore other early and immediate regulators.
|ISBN||1098-5549 (Electronic) 0270-7306 (Linking)|
|Authors||Ma, X.; Yang, P.; Kaplan, W. H.; Lee, B. H.; Wu, L. E.; Yang, J. Y.; Yasunaga, M.; Sato, K.; Chisholm, D. J.; James, D. E.;|
|Responsible Garvan Author|
|Publisher Name||MOLECULAR AND CELLULAR BIOLOGY|
|URL link to publisher's version||http://www.ncbi.nlm.nih.gov/pubmed/25047837|
|OpenAccess link to author's accepted manuscript version||https://publications.gimr.garvan.org.au/open-access/12380|