当前位置：
X-MOL 学术
›
BBA Mol. Cell Biol. Lipids
›
论文详情
Our official English website, www.x-mol.net, welcomes your
feedback! (Note: you will need to create a separate account there.)
Automated untargeted stable isotope assisted lipidomics of liver cells on high glucose shows alteration of sphingolipid kinetics.
Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids ( IF 3.9 ) Pub Date : 2020-02-08 , DOI: 10.1016/j.bbalip.2020.158656 Davide Noto 1 , Francesca Di Gaudio 2 , Ida Grazia Altieri 1 , Angelo Baldassare Cefalù 1 , Sergio Indelicato 3 , Francesca Fayer 1 , Rossella Spina 1 , Chiara Scrimali 1 , Antonina Giammanco 1 , Alessandro Mattina 1 , Serena Indelicato 3 , Massimiliano Greco 3 , David Bongiorno 3 , Maurizio Averna 1
Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids ( IF 3.9 ) Pub Date : 2020-02-08 , DOI: 10.1016/j.bbalip.2020.158656 Davide Noto 1 , Francesca Di Gaudio 2 , Ida Grazia Altieri 1 , Angelo Baldassare Cefalù 1 , Sergio Indelicato 3 , Francesca Fayer 1 , Rossella Spina 1 , Chiara Scrimali 1 , Antonina Giammanco 1 , Alessandro Mattina 1 , Serena Indelicato 3 , Massimiliano Greco 3 , David Bongiorno 3 , Maurizio Averna 1
Affiliation
|
Untargeted lipidomics is a powerful tool to discover new biomarkers and to understand the physiology and pathology of lipids. The use of stable isotopes as tracers to investigate the kinetics of lipids is another tool able to supply dynamic information on lipid synthesis and catabolism. Coupling the two methodology is then very appealing in the study of lipid metabolism. The main issue to face is to perform thousands of calculations in order to obtain kinetic parameters starting from the MS raw data. An automated computerized routine able to do accomplish such task is presented in this paper. We analyzed the lipid kinetics of palmitic acid (PA) in hepatoma liver cells cultured in vitro in which insulin resistance has been induced by high glucose supplementation. The deuterated palmitate tracer (d5PA) was administered as a bolus and the cells were harvested daily for 48 h. 5dPA was incorporated into 326 monoisotopic compounds and in 84 of their [M + 1] isotopologues detected by high resolution orbitrap MS. The differences between the kinetics curves showed that at least four long chain triglycerides (TG) species incorporated more PA in glucose treated cells, while phosphocholines, sphingomyelins, mono- and di-glycerides and ceramides (Cer) incorporated less tracer under glucose treatment. Nevertheless, Cer amount was increased by glucose treatment. In conclusion we developed an automated powerful algorithm able to model simultaneously hundreds of kinetic curves obtained in a cell culture spiked with a stable isotope tracer, and to analyze the difference between the two different cell models.
中文翻译：
在高葡萄糖条件下肝细胞的自动无靶稳定同位素辅助脂质组学显示了鞘脂动力学的改变。
非靶向脂质组学是发现新生物标记并了解脂质的生理学和病理学的有力工具。使用稳定同位素作为示踪剂研究脂质的动力学是另一个能够提供有关脂质合成和分解代谢的动态信息的工具。因此，将两种方法结合起来在脂类代谢研究中非常有吸引力。面临的主要问题是要执行数千次计算，以便从MS原始数据开始获得动力学参数。本文介绍了能够完成此类任务的自动化计算机程序。我们分析了在体外培养的肝癌肝细胞中棕榈酸（PA）的脂质动力学，其中高糖补充已诱导了胰岛素抵抗。氘化棕榈酸酯示踪剂（d5PA）以大剂量给药，每天收获细胞48小时。将5dPA掺入326种单一同位素化合物中，并通过高分辨率orbitrap MS检测到84种[M +1]同位素。动力学曲线之间的差异表明，在葡萄糖处理的细胞中，至少有四个长链甘油三酸酯（TG）掺入了更多的PA，而在葡萄糖处理下，磷酸胆碱，鞘磷脂，单和双甘油酯和神经酰胺（Cer）掺入的示踪剂较少。然而，通过葡萄糖处理增加了Cer量。总之，我们开发了一种自动强大的算法，能够同时对在掺有稳定同位素示踪剂的细胞培养物中获得的数百条动力学曲线进行建模，并分析两种不同细胞模型之间的差异。
更新日期：2020-02-10
中文翻译：
在高葡萄糖条件下肝细胞的自动无靶稳定同位素辅助脂质组学显示了鞘脂动力学的改变。
非靶向脂质组学是发现新生物标记并了解脂质的生理学和病理学的有力工具。使用稳定同位素作为示踪剂研究脂质的动力学是另一个能够提供有关脂质合成和分解代谢的动态信息的工具。因此，将两种方法结合起来在脂类代谢研究中非常有吸引力。面临的主要问题是要执行数千次计算，以便从MS原始数据开始获得动力学参数。本文介绍了能够完成此类任务的自动化计算机程序。我们分析了在体外培养的肝癌肝细胞中棕榈酸（PA）的脂质动力学，其中高糖补充已诱导了胰岛素抵抗。氘化棕榈酸酯示踪剂（d5PA）以大剂量给药，每天收获细胞48小时。将5dPA掺入326种单一同位素化合物中，并通过高分辨率orbitrap MS检测到84种[M +1]同位素。动力学曲线之间的差异表明，在葡萄糖处理的细胞中，至少有四个长链甘油三酸酯（TG）掺入了更多的PA，而在葡萄糖处理下，磷酸胆碱，鞘磷脂，单和双甘油酯和神经酰胺（Cer）掺入的示踪剂较少。然而，通过葡萄糖处理增加了Cer量。总之，我们开发了一种自动强大的算法，能够同时对在掺有稳定同位素示踪剂的细胞培养物中获得的数百条动力学曲线进行建模，并分析两种不同细胞模型之间的差异。
京公网安备 11010802027423号