Our working hypothesis is that excessive FFA flux from adipose tissue raises serum triglyceride concentrations and leads to other manifestations of the IRS. FFA flux is chronically elevated in insulin resistant subjects due to the insensitivity (i.e., resistance) of their adipocytes to the anti-lipolytic effects of insulin. Released FFA (especially from visceral adipose depots) stimulate hepatic triglyceride synthesis, leading to elevated serum triglyceride levels which subsequently contribute to reduced HDL-C and increased small, dense LDL concentrations. In addition, a high FFA flux can interfere with whole body glucose disposal. If this hypothesis is true, then interventions that improve adipocyte insulin sensitivity may be expected to improve a spectrum of risk factors associated with the insulin resistant state.