Varela Lourdes M, López Sergio, Ortega-Gómez Almudena, Bermúdez Beatriz, Buers Insa, Robenek Horst, Muriana Francisco J G, Abia Rocío
Cellular and Molecular Nutrition, Instituto de la Grasa, Consejo Superior de Investigaciones Científicas, Seville, Spain.
Department of Pharmacology, School of Pharmacy, University of Seville, Sevilla, Spain.
J Nutr Biochem. 2015 Apr;26(4):327-36. doi: 10.1016/j.jnutbio.2014.11.007. Epub 2014 Dec 15.
Lipid accumulation in macrophages contributes to atherosclerosis. Within macrophages, lipids are stored in lipid droplets (LDs); perilipin-2 and perilipin-3 are the main LD-associated proteins. Postprandial triglyceride (TG)-rich lipoproteins induce LD accumulation in macrophages. The role of postprandial lipoproteins in perilipin-2 and perilipin-3 regulation was studied. TG-rich lipoproteins (TRLs) induced the levels of intracellular TGs, LDs and perilipin-2 protein expression in THP-1 macrophages and in Apoe(-/-) mice bone-marrow-derived macrophages with low and high basal levels of TGs. Perilipin-3 was only synthesized in mice macrophages with low basal levels of TGs. The regulation was dependent on the fatty acid composition of the lipoproteins; monounsaturated and polyunsaturated fatty acids (PUFAs) more strongly attenuated these effects compared with saturated fatty acids. In THP-1 macrophages, immunofluorescence microscopy and freeze-fracture immunogold labeling indicated that the lipoproteins translocated perilipin-3 from the cytoplasm to the LD surface; only the lipoproteins that were rich in PUFAs suppressed this effect. Chemical inhibition showed that lipoproteins induced perilipin-2 protein expression through the peroxisome proliferator-activated nuclear receptor (PPAR) PPARα and PPARγ pathways. Overall, our data indicate that postprandial TRLs may be involved in atherosclerotic plaque formation through the regulation of perilipin-2 and perilipin-3 proteins in macrophages. Because the fatty acid composition of the lipoproteins is dependent on the type of fat consumed, the ingestion of olive oil, which is rich in monounsaturated fatty acids, and fish oil, which is rich in omega-3 fatty acids, can be considered a good nutritional strategy to reduce the risk of atherosclerosis by LD-associated proteins decrease.
巨噬细胞中的脂质积累会导致动脉粥样硬化。在巨噬细胞内，脂质存储在脂滴（LDs）中；围脂滴蛋白-2和围脂滴蛋白-3是主要的与脂滴相关的蛋白质。餐后富含甘油三酯（TG）的脂蛋白会诱导巨噬细胞中脂滴的积累。研究了餐后脂蛋白在围脂滴蛋白-2和围脂滴蛋白-3调节中的作用。富含TG的脂蛋白（TRLs）在基础TG水平低和高的THP-1巨噬细胞以及Apoe(-/-)小鼠骨髓来源的巨噬细胞中诱导细胞内TG、脂滴水平以及围脂滴蛋白-2蛋白表达。围脂滴蛋白-3仅在基础TG水平低的小鼠巨噬细胞中合成。这种调节取决于脂蛋白的脂肪酸组成；与饱和脂肪酸相比，单不饱和脂肪酸和多不饱和脂肪酸（PUFAs）更强烈地减弱了这些作用。在THP-1巨噬细胞中，免疫荧光显微镜和冷冻断裂免疫金标记表明脂蛋白将围脂滴蛋白-3从细胞质转运到脂滴表面；只有富含PUFAs的脂蛋白抑制了这种作用。化学抑制表明脂蛋白通过过氧化物酶体增殖物激活核受体（PPAR）PPARα和PPARγ途径诱导围脂滴蛋白-2蛋白表达。总体而言，我们的数据表明餐后TRLs可能通过调节巨噬细胞中的围脂滴蛋白-2和围脂滴蛋白-3蛋白参与动脉粥样硬化斑块的形成。由于脂蛋白的脂肪酸组成取决于所摄入脂肪的类型，摄入富含单不饱和脂肪酸的橄榄油和富含ω-3脂肪酸的鱼油可被视为一种良好的营养策略，通过降低与脂滴相关的蛋白质来降低动脉粥样硬化风险。
