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Abstract
BackgroundPolyunsaturated fatty acids (PUFAs) have positive effect on the regulation of plasma lipids. But the mechanism for them to modulate lipid homeostasis in macrophage is still unclear. In this study, we employed PUFA to pretreat macrophages and evaluated the variations of lipid droplet (LD) content, lipid composition, and expressions of LD-associated genes in macrophage-derived foam cells.MethodTHP-1-derived macrophages or human peripheral blood monocyte-derived macrophages were pre-treated with four non-esterified fatty acids (NEFAs) separately: saturated fatty acid (SFA)-palmitic acid (PA), monounsaturated fatty acids (MUFAs)-oleic acid (OA), PUFAs-linoleic acid (LA) and eicosapentaenoic acid (EPA). Intracellular lipid content and cholesterol efflux were analyzed in THP-1 macrophage-derived foam cells. Related gene expressions were detected by quantitative real-time PCR.ResultsPUFA pre-treatment reduced cholesterol content in foam cells and increased cholesterol efflux to lipid-free apoAI in conditioned medium compared with PA or OA group. Cell death-inducing DFF45 like effector (CIDE) and Perilipin-Adipophilin-TIP47 (PAT) family members, as LD-associated proteins, showed specific gene expression profiles after PUFA pre-treatment. These results may help to explain the process of lipid metabolism within foam cells.ConclusionPUFA (LA or EPA) had a potential protective effect against cholesterol accumulation. The specific expressions of CIDE and PAT genes may provide clues to explore the protective mechanism of PUFA in foam cells.
Highlights
Polyunsaturated fatty acids (PUFAs) have positive effect on the regulation of plasma lipids
PUFA pre-treatment reduced cholesterol content in foam cells and increased cholesterol efflux to lipid-free apolipoprotein AI (apoAI) in conditioned medium compared with palmitic acid (PA) or oleic acid (OA) group
The specific expressions of Cell death-inducing DFF45 like effector (CIDE) and PAT genes may provide clues to explore the protective mechanism of PUFA in foam cells
Summary
Polyunsaturated fatty acids (PUFAs) have positive effect on the regulation of plasma lipids. The mechanism for them to modulate lipid homeostasis in macrophage is still unclear. We employed PUFA to pretreat macrophages and evaluated the variations of lipid droplet (LD) content, lipid composition, and expressions of LD-associated genes in macrophage-derived foam cells. PUFAs are essential components in lipid metabolism. It has been reported that PUFAs can affect lipid storage and reduce the risk factors of cardiovascular diseases [1]. The potential role of PUFA in the formation of fatty streak and atherosclerotic plaque is not yet clear. The molecular mechanism for PUFA-induced lipid influx and efflux in foam cells is inconclusive. Abnormal lipid deposition in the intima of artery wall leads to the formation of fatty streak.
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