Comprehensive and quantitative analysis of white and brown adipose tissue by shotgun lipidomics

Comprehensive and quantitative analysis of white and brown adipose tissue by shotgun lipidomics
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DOI:
10.1016/j.molmet.2019.01.009
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发表时间:
2019-04-01
影响因子:
8.1
通讯作者:
Coskun, Uenal
Coskun, Uenal
中科院分区:
医学1区
文献类型:
--
作者:
Grzybek, Michal;Palladini, Alessandra;Coskun, Uenal

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目的:鸟枪式脂质组学能够对组织和体液中的脂质进行广泛的分析。每个样本都需要适当的提取和处理程序,以确保脂质组的良好覆盖和可重现定量。脂肪组织(adipose tissue,AT)因其参与肥胖相关的病理过程而成为研究热点。然而,AT脂质组的定量是特别具有挑战性的,这是由于三酰甘油酯的优势,这会引起其余脂质类的高离子抑制。我们提出了一种新的和有效的方法,用于AT的鸟枪脂质组学,该系统为目标样本量身定制脂质提取程序,具有高重现性,对于所有脂质类别,线性动态范围至少为4个数量级。利用这种方法,我们观察了组织特异性和饮食相关的差异,在三个AT类型(棕色,性腺,腹股沟皮下)从瘦和肥胖小鼠。棕色AT表现出独特的脂质组学特征,具有最大的脂质类多样性,并通过改变其脂质组成来响应高脂饮食,其向白色AT转变。此外,饮食诱导的肥胖促进了脂质组的整体重塑,其中所有三种AT类型的特征是更长和更不饱和的甘油三酯和磷脂物质的显着增加。本文提出的方法有助于AT的可再现的系统脂质组学分析,并且可以与(前)临床研究中使用的进一步的组学方法整合,以促进对肥胖相关疾病发病机制中所涉及的分子代谢动力学的理解。(C)2019年,任作家。由爱思唯尔有限公司出版。
Objective: Shotgun lipidomics enables an extensive analysis of lipids from tissues and fluids. Each specimen requires appropriate extraction and processing procedures to ensure good coverage and reproducible quantification of the lipidome. Adipose tissue (AT) has become a research focus with regard to its involvement in obesity-related pathologies. However, the quantification of the AT lipidome is particularly challenging due to the predominance of triacylglycerides, which elicit high ion suppression of the remaining lipid classes.Methods: We present a new and validated method for shotgun lipidomics of AT, which tailors the lipid extraction procedure to the target specimen and features high reproducibility with a linear dynamic range of at least 4 orders of magnitude for all lipid classes.Results: Utilizing this method, we observed tissue-specific and diet-related differences in three AT types (brown, gonadal, inguinal subcutaneous) from lean and obese mice. Brown AT exhibited a distinct lipidomic profile with the greatest lipid class diversity and responded to high-fat diet by altering its lipid composition, which shifted towards that of white AT. Moreover, diet-induced obesity promoted an overall remodeling of the lipidome, where all three AT types featured a significant increase in longer and more unsaturated triacylglyceride and phospholipid species.Conclusions: The here presented method facilitates reproducible systematic lipidomic profiling of AT and could be integrated with further - omics approaches used in (pre-) clinical research, in order to advance the understanding of the molecular metabolic dynamics involved in the pathogenesis of obesity-associated disorders. (C) 2019 The Authors. Published by Elsevier GmbH.