State Key Laboratory of Cancer Biology and Department of Pathology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Lipids Health Dis. 2013 Jul 23;12:111. doi: 10.1186/1476-511X-12-111.
Polyunsaturated 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.
THP-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.
PUFA 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.
PUFA (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.
多不饱和脂肪酸(PUFAs)对调节血浆脂质有积极作用。但它们调节巨噬细胞脂类稳态的机制尚不清楚。在这项研究中,我们用 PUFAs 预处理巨噬细胞,评估了巨噬细胞源性泡沫细胞中脂滴(LD)含量、脂质组成和 LD 相关基因表达的变化。
分别用四种非酯化脂肪酸(NEFAs)预处理 THP-1 衍生的巨噬细胞或人外周血单核细胞衍生的巨噬细胞:饱和脂肪酸(SFA)-棕榈酸(PA)、单不饱和脂肪酸(MUFAs)-油酸(OA)、PUFAs-亚油酸(LA)和二十碳五烯酸(EPA)。在 THP-1 巨噬细胞源性泡沫细胞中分析细胞内脂质含量和胆固醇流出。通过实时定量 PCR 检测相关基因表达。
与 PA 或 OA 组相比,PUFA 预处理降低了泡沫细胞中的胆固醇含量,并增加了胆固醇向无脂载脂蛋白 AI 的流出。作为 LD 相关蛋白的细胞死亡诱导 DFF45 样效应物(CIDE)和 Perilipin-Adipophilin-TIP47(PAT)家族成员的表达在 PUFAs 预处理后显示出特定的基因表达谱。这些结果可能有助于解释泡沫细胞内的脂质代谢过程。
PUFA(LA 或 EPA)对胆固醇积累有潜在的保护作用。CIDE 和 PAT 基因的特定表达可能为探索 PUFAs 在泡沫细胞中的保护机制提供线索。