In vivo metabolic fingerprinting of neutral lipids with hyperspectral stimulated Raman scattering microscopy.
In vivo metabolic fingerprinting of neutral lipids with hyperspectral stimulated Raman scattering microscopy.
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DOI：
10.1021/ja504199s
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发表时间：
2014-06-18
影响因子：
15
通讯作者：
Wang, Meng C.
中科院分区：
文献类型：
--
作者：
Fu, Dan;Yu, Yong;Folick, Andrew;Currie, Erin;Farese, Robert V., Jr.;Tsai, Tsung-Huang;Xie, Xiaoliang Sunney;Wang, Meng C.
代谢指纹图谱提供了关于细胞和组织的生理病理状态的有价值的信息。传统的成像质谱学和磁共振成像由于缺乏空间分辨率或无法进行活细胞成像，无法在亚细胞水平上探测代谢物的时空动力学。在这里，我们报告了一种基于高光谱受激拉曼散射(HsSRS)的互补代谢成像技术。我们展示了使用hsSRS成像来定量细胞和组织中两种主要的中性脂质：胆固醇酯和三酰甘油。我们的成像结果揭示了以前未知的与肥胖和脂肪性肝炎相关的脂质成分的变化。我们进一步使用稳定同位素标记通过hsSRS成像跟踪活细胞和活秀丽线虫中脂肪酸的代谢动态。我们发现不饱和脂肪酸优先吸收到脂肪储存中，而饱和脂肪酸在肝细胞中表现出毒性。与之前的假设不同，对活的线虫体内的氚标记的饱和脂肪酸和不饱和脂肪酸的同时代谢指纹图谱显示，两者之间缺乏相互作用。我们的发现为在活细胞和生物体中追踪中性脂质及其前体的代谢提供了新的方法，并可能作为其他代谢物的代谢指纹图谱的一般方法。
Metabolic fingerprinting provides valuable information on the physiopathological states of cells and tissues. Traditional imaging mass spectrometry and magnetic resonance imaging are unable to probe the spatial-temporal dynamics of metabolites at the subcellular level due to either lack of spatial resolution or inability to perform live cell imaging. Here we report a complementary metabolic imaging technique that is based on hyperspectral stimulated Raman scattering (hsSRS). We demonstrated the use of hsSRS imaging in quantifying two major neutral lipids: cholesteryl ester and triacylglycerol in cells and tissues. Our imaging results revealed previously unknown changes of lipid composition associated with obesity and steatohepatitis. We further used stable-isotope labeling to trace the metabolic dynamics of fatty acids in live cells and live Caenorhabditis elegans with hsSRS imaging. We found that unsaturated fatty acid has preferential uptake into lipid storage while saturated fatty acid exhibits toxicity in hepatic cells. Simultaneous metabolic fingerprinting of deuterium-labeled saturated and unsaturated fatty acids in living C. elegans revealed that there is a lack of interaction between the two, unlike previously hypothesized. Our findings provide new approaches for metabolic tracing of neutral lipids and their precursors in living cells and organisms, and could potentially serve as a general approach for metabolic fingerprinting of other metabolites.
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影响因子：
3.3
作者：
Fu, Dan;Holtom, Gary;Freudiger, Christian;Zhang, Xu;Xie, Xiaoliang Sunney
通讯作者：
Xie, Xiaoliang Sunney
影响因子：
64.8
作者：
Steinhauser, Matthew L.;Bailey, Andrew P.;Senyo, Samuel E.;Guillermier, Christelle;Perlstein, Todd S.;Gould, Alex P.;Lee, Richard T.;Lechene, Claude P.
通讯作者：
Lechene, Claude P.
DOI：
10.1111/j.1440-1746.2008.05733.x
发表时间：
2009-05-01
影响因子：
4.1
作者：
Ricchi, Matteo;Odoardi, Maria Rosaria;Loria, Paola
通讯作者：
Loria, Paola
影响因子：
9.2
作者：
Herms, Albert;Bosch, Marta;Ariotti, Nicholas;Reddy, Babu J. N.;Fajardo, Alba;Fernandez-Vidal, Andrea;Alvarez-Guaita, Anna;Fernandez-Rojo, Manuel Alejandro;Rentero, Carles;Tebar, Francesc;Enrich, Carlos;Geli, Maria-Isabel;Parton, Robert G.;Gross, Steven P.;Pol, Albert
通讯作者：
Pol, Albert
影响因子：
3.2
作者：
Jensen-Pergakes, K;Guo, ZM;Bard, M
通讯作者：
Bard, M