Sterol regulatory element-binding protein (SREBP)-1: gene regulatory target for insulin resistance?

The combined appearance of different cardiovascular risk factors seems to be more prevalent in individuals with decreased insulin sensitivity and increased visceral obesity, thereby being components of the so-called metabolic syndrome. Alterations in transcription factors result in complex dysregulation of gene expression, which might be the key to understanding insulin resistance-associated clinical clustering of coronary risk factors at the cellular or gene regulatory level. Recent examples are peroxisome proliferator-activated receptors and sterol regulatory element-binding proteins (SREBPs), which also appear to be novel drug targets. The authors have recently shown that SREBPs are substrates of mitogen-activated protein kinases, and propose that SREBP-1 might play a role in the development of cellular features belonging to lipotoxicity and, possibly, syndrome X.