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Mapping Lipogenic Flux: A Gold LDI-MS Approach for Imaging Neutral Lipid Kinetics.
Journal of the American Society for Mass Spectrometry ( IF 3.1 ) Pub Date : 2020-09-01 , DOI: 10.1021/jasms.0c00199
Daniel P Downes 1 , Wendy Zhong 2 , Ji Zhang 3 , Bingming Chen 4 , Santhosh Satapati 3 , Daniel Metzger 3 , Guillermo Godinez 3 , Julie Lao 3 , Payal R Sheth 1 , David G McLaren 1 , Saswata Talukdar 3 , Stephen F Previs 1
Affiliation  

Spatial characterization of triglyceride metabolism is an area of significant interest which can be enabled by mass spectrometry imaging via recent advances in neutral lipid laser desorption analytical approaches. Here, we extend recent advancements in gold-assisted neutral lipid imaging and demonstrate the potential to map lipid flux in rodents. We address here critical issues surrounding the analytical configuration and interpretation of the data for a group of select triglycerides. Specifically, we examined how the signal intensity and spatial resolution would impact the apparent isotope ratio in a given analyte (which is an important consideration when performing MS based kinetics studies of this kind) with attention given to molecular ions and not fragments. We evaluated the analytics by contrasting lipid flux in well characterized mouse models, including fed vs fed states and different dietary perturbations. In total, the experimental paradigm described here should enable studies of hepatic lipogenesis; presumably, this logic can be enhanced via the inclusion of ion mobility and/or fragmentation. Although this study was carried out in robust models of liver lipogenesis, we expect that the model system could be expanded to a variety of tissues where zonated (or heterogeneous) lipid synthesis may occur, including solid tumor metabolism.

中文翻译:

映射脂肪生成通量:用于中性脂质动力学成像的黄金 LDI-MS 方法。

甘油三酯代谢的空间表征是一个重要的领域,可以通过中性脂质激光解吸分析方法的最新进展通过质谱成像来实现。在这里,我们扩展了金辅助中性脂质成像的最新进展,并证明了绘制啮齿动物脂质通量的潜力。我们在此解决围绕一组精选甘油三酯的数据的分析配置和解释的关键问题。具体而言,我们研究了信号强度和空间分辨率如何影响给定分析物的表观同位素比(这是进行此类基于 MS 的动力学研究时的一个重要考虑因素),同时关注分子离子而非碎片。我们通过对比充分表征的小鼠模型中的脂质通量来评估分析,包括进食与进食状态和不同的饮食扰动。总的来说,这里描述的实验范式应该能够研究肝脏脂肪生成;据推测,可以通过包含离子迁移率和/或碎片来增强这种逻辑。尽管这项研究是在强大的肝脏脂肪生成模型中进行的,但我们预计该模型系统可以扩展到可能发生分区(或异质)脂质合成的各种组织,包括实体瘤代谢。
更新日期:2020-09-01
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