Peroxisome proliferator-activated receptor α and γ agonists upregulate human macrophage lipoprotein lipase expression

Peroxisome proliferator-activated receptors (PPARs) are transcriptional factors which mediate pleiotropic effects including regulation of genes involved in lipid metabolism and control of inflammation. In the present study, we measured the in vitro effects of PPARα and γ ligands on macrophage lipoprotein lipase (LPL) expression. Human monocyte-derived macrophages (MDM) were cultured for 1–3 days in the presence of PPARα and γ ligands. At the end of these incubation periods, extracellular LPL immunoreactive mass/activity and LPL mRNA levels were measured. Incubation of human MDM with PPARα and γ ligands stimulated, in a time- and dose-dependent manner, human MDM LPL mass and activity. These agents also significantly increased macrophage LPL mRNA expression. In THP-1 cells treated with PPARα and γ ligands, enhanced nuclear protein binding to the peroxisome proliferator responsive element (PPRE) of the human LPL promoter was observed. Furthermore, in these cells, a decreased rate of decay of LPL mRNA was documented. Overall, these results demonstrate that PPARα and γ activators increase macrophage LPL secretion. Given the proatherogenic effect of vascular wall LPL, better understanding of the role of PPARs in the regulation of macrophage LPL expression could lead to the development of new approaches in the prevention and treatment of atherosclerosis.