Global transcriptome profiling identifies KLF15 and SLC25A10 as regulators of adipocytes insulin sensitivity in obese women [siRNA]

The aim of this study was to identify new genes controlling insulin sensitivity in adipocytes from obese women with either insulin-resistant (OIR) or -sensitive (OIS) adipocytes. 432 genes were differentially expressed between the OIR and OIS group (FDR <5%). These genes are enriched in pathways related to glucose and amino acid metabolism, cellular respiration, and insulin signaling. Two IR-associated genes, KLF15 and SLC25A10, were selected for functional evaluation. Insulin sensitivity was determined by measuring lipogenesis in isolated adipocytes from abdominal subcutaneous white adipose tissue (WAT). Knockdown of KLF15 and SLC25A10 genes using siRNA inhibited insulin-stimulated lipogenesis in in vitro differentiated primary adipocytes. Transcriptome profiling of siRNA treated cells suggested that KLF15 controlled insulin stimulated lipogenesis by influencing expression of PPARG, PXMP2, AQP7, LPL and genes in the mitochondrial respiratory chain. Knockdown of SLC25A10 had modest impact on the transcriptome. Significance analysis of microarrays (SAM) was use to compare the difference in gene expression between groups.