High-resolution imaging of dietary lipids in cells and tissues by NanoSIMS analysis
High-resolution imaging of dietary lipids in cells and tissues by NanoSIMS analysis
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DOI：
10.1194/jlr.m053363
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发表时间：
2014-10-01
影响因子：
6.5
通讯作者：
Young, Stephen G.
中科院分区：
文献类型：
--
作者：
Jiang, Haibo;Goulbourne, Chris N.;Young, Stephen G.
纳米级二次离子MS（NanoSIMS）成像使得能够以50 nm的横向分辨率可视化细胞和组织中稳定的同位素标记的脂质。在这里，我们报告了使用NanoSIMS成像来可视化小鼠细胞和组织中的脂质。通过灌胃给小鼠施用稳定的同位素标记的脂肪酸后，NanoSIMS成像使我们能够可视化肠上皮细胞中细胞溶质脂滴中的中性脂质，肠上皮细胞基底外侧表面的乳糜微粒以及心肌细胞和脂肪细胞中的脂滴。在注射稳定的同位素富集的富含磷脂酰肌醇的脂蛋白（TRL）后，NanoSIMS成像记录了脂质向实质细胞中的胞质脂滴的递送。使用背散射电子（BSE）和NanoSIMS成像的组合，可以将NanoSIMS提供的化学数据与细胞形态的高分辨率BSE图像相关联。这种联合成像方法使我们能够沿着心脏毛细血管的管腔面和心脏毛细血管内皮细胞内的脂质可视化稳定的同位素富集TRL沿着。我们还观察到心脏毛细血管内皮下空间内的TRL的例子。NanoSIMS成像提供了在糖基磷脂酰肌醇锚定的HDL结合蛋白1缺陷的小鼠中脂质从血浆LP到脂肪细胞和心肌细胞的缺陷转运的证据。
Nanoscale secondary ion MS (NanoSIMS) imaging makes it possible to visualize stable isotope-labeled lipids in cells and tissues at 50 nm lateral resolution. Here we report the use of NanoSIMS imaging to visualize lipids in mouse cells and tissues. After administering stable isotope-labeled fatty acids to mice by gavage, NanoSIMS imaging allowed us to visualize neutral lipids in cytosolic lipid droplets in intestinal enterocytes, chylomicrons at the basolateral surface of enterocytes, and lipid droplets in cardiomyocytes and adipocytes. After an injection of stable isotope-enriched triglyceride-rich lipoproteins (TRLs), NanoSIMS imaging documented delivery of lipids to cytosolic lipid droplets in parenchymal cells. Using a combination of backscattered electron (BSE) and NanoSIMS imaging, it was possible to correlate the chemical data provided by NanoSIMS with high-resolution BSE images of cell morphology. This combined imaging approach allowed us to visualize stable isotope-enriched TRLs along the luminal face of heart capillaries and the lipids within heart capillary endothelial cells. We also observed examples of TRLs within the subendothelial spaces of heart capillaries. NanoSIMS imaging provided evidence of defective transport of lipids from the plasma LPs to adipocytes and cardiomyocytes in mice deficient in glycosylphosphatidylinositol-anchored HDL binding protein 1.