Adipocyte‐derived Lipoprotein Lipase Induces Macrophage Activation and Monocyte Adhesion: Role of Fatty Acids

OBJECTIVE: We evaluated the effect of adipocyte-derived lipoprotein lipase (LPL) on macrophage activation and monocyte adhesion and the role of fatty acids in these effects. RESEARCH METHODS AND PROCEDURES: 3T3-L1 adipocytes were incubated with heparin or insulin to induce LPL secretion; then adipocyte conditioned media (CM) were added to cultured J774 macrophages or human aortic endothelial cells (HAECs). Macrophage cytokine production and monocyte adhesion to HAECs were determined. RESULTS: Incubation of macrophages with heparin- or insulin-treated adipocyte CM increased tumor necrosis factor alpha, interleukin-6, and nitric oxide production by these cells. LPL neutralization and heparinase treatment prevented these effects. Addition of active LPL or palmitate to cultured macrophages replicated these effects. Blockade of leptin also reduced the effect of insulin-treated adipocyte CM on macrophage inflammatory changes. Induction of macrophage cytokine secretion by leptin was prevented by LPL immunoneutralization. Finally, addition of CM of heparin- or insulin-treated adipocytes to HAECs stimulated monocyte adhesion to these cells, an effect that was abrogated by an anti-LPL antibody. This effect was reproduced by treating HAECs with active LPL or palmitate. DISCUSSION: These results point to an effect of LPL-mediated lipolysis in macrophage activation and monocyte adhesion.