KLF Regulation of Insulin Pathway Genes.

Alteration in lipid metabolism can result in fat accumulation in adipose tissues, which may lead to two most important human diseases, obesity and diabetes. A shift in lipid metabolism deregulates signaling pathways which regulates obesity and/or diabetes. In this study, we examined the components of insulin/ TGF-β pathways and their genetic interaction with Krüppel-like transcription factors (KLFs). Their role in energy homeostasis were discussed. We separately created klf/daf genes double mutants by carrying out klfs RNAi on daf-2 (e1391), daf-4 (e1364), daf-7 (e1372); dpy-1 (e1), daf-14 (m77), daf-16 (mgDf50) mutants. And then conducted Oil O Red staining to assay the klf/daf RNAi worms for fat deposits and examine genetic interaction between klfs and daf genes. The results showed that worms bearing klf-1, 2, or 3 and daf-2, or daf-4 mutations deposit large, but similar fat levels as individual mutants. The results suggested that they target the same molecular pathway of fat storage. klf-1, 2 or 3 RNAi /daf-7 worms showed higher fat deposits in klf-1, 2, or 3 RNAi/daf-7 worms than klf-1, 2, or 3 RNAi or daf-7 mutants alone, which showed a functional interaction between klfs and daf-7 in perhaps TGF-β-like pathway. Altogether our study suggests a direct role of klfs in insulin signaling pathway.