Rat glomerular mesangial cells (MC) become lipid laden foam cells when they are exposed to IGF-1. IGF-1 increased accumulation of triglyceride 2.5-fold in MC after 7 days. TG accumulation resulted from enhanced macropinocytosis and decreased efflux secondary to a 40- 50% reduction in PPAR. There was no evidence for primary or secondary changes in cholesterol or TG synthesis, increased uptake by LDL or scavenger receptors, or reduced efflux via ABCA-1. Although the lipid moiety taken up can be influenced by the concentration of cholesterol or triglyceride (TG) in the medium, in standard medium MC preferentially accumulate TG. TG rich MC foam cells fail to contract in response to angiotensin II (Berfield AK et al, Kidney Int, 62:1229, 2002); however their migratory response to insulin-like growth factor binding protein-5 is unaffected. This differs from cholesterol loading which impairs both phagocytosis and migration. These findings have important implications for understanding the mechanisms that contribute to lipid accumulation in MC and the functional consequences of different forms of foam cells. These observations are relevant to understanding vascular disease and progressive renal diseases that are accelerated by abnormalities of lipid metabolism.