The ectopic fat theory has gained a significant body of supporting experimental data in the last few years. Yet, much investigational work remains to be done to precisely elucidate the mechanisms by which ectopic fat produce the downstream abnormalities of insulin resistance, hyperglycemia, atherogenic dyslipidemia, and hypertension observed in the metabolic syndrome. Such knowledge is needed not just to further validate the ectopic fat theory, but also to facilitate the design of pharmacological agents that specifically target the pathophysiology of the metabolic syndrome. This is particularly critical because currently there is no commercially available pharmacological treatment that completely reverses the metabolic syndrome, and physicians must rely on multiple drugs to individually treat the multiple abnormalities seen in the metabolic syndrome, i.e., dyslipidemia, hypertension, and insulin resistance. As a result, a significant proportion of the adult population with metabolic syndrome must currently rely on polypharmacy for treatment. In principle, it could be proposed that nonpharmacological treatment by means of weight loss and physical activity is all that is needed to contain the epidemics of obesity and the metabolic syndrome. However, on pragmatic terms, given the formidable challenges of attaining and then sustaining weight loss, there is a need for effective adjunctive pharmacological treatments for obesity and obesity-related insulin resistance. [ABSTRACT FROM AUTHOR]