Inhibition of SCD activity enhances inflammation in RAW264.7 macrophages but improves cholesterol trafficking

Abstract

Obesity is a major risk factor for atherosclerosis. Loss of stearoyl CoA desaturase (SCD) 1 in mice has been shown to protect mice from obesity. However, the role of SCD in atherosclerosis has not yet been fully understood. Macrophage inflammation is a key characteristic of atherosclerosis. Here, we tested the effects of SCD activity on the inflammation and cholesterol transport in RAW264.7 macrophages. Inhibition of the overall SCD activity by A939572, a pharmacological inhibitor targeting the catalytic domain of the enzyme, enhances the induction of inflammatory genes upon LPS treatment in RAW cells, which is prevented by addition of oleate (18:1n9) or palmitoleate (16:1n7), two products of SCD activity. While the total free cholesterol level is elevated in RAW cells treated with A939572, the uptake of oxLDL is, however, reduced. In addition, cholesterol efflux is increased with treatment of A939572 in these macrophages. The above results indicate that although inhibition of SCD activity promotes macrophage inflammation, it improves cholesterol trafficking in RAW macrophages. Thus, SCD might regulate inflammation and cholesterol trafficking through distinct pathways in macrophages.