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.