Paul Langerhans Institute Dresden of the Helmholtz Zentrum Munich at the University Clinic Carl Gustav Carus, TU Dresden, Dresden, Germany; German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany.
Institute for Clinical Chemistry and Laboratory Medicine, Faculty of Medicine, TU Dresden, Dresden, Germany.
Mol Metab. 2019 Apr;22:12-20. doi: 10.1016/j.molmet.2019.01.009. Epub 2019 Jan 30.
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.
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.
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.
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.
shotgun 脂质组学能够广泛分析组织和体液中的脂质。每个标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复的定量。脂肪组织（AT）因其与肥胖相关疾病的关系而成为研究热点。然而，由于三酰甘油的优势，使得 AT 脂质组的定量特别具有挑战性，因为三酰甘油会对其余脂质类别产生高离子抑制。
我们提出了一种新的、经过验证的 AT shotgun 脂质组学方法，该方法根据目标标本调整脂质提取程序，并具有高重现性，所有脂质类别的线性动态范围至少为 4 个数量级。
利用该方法，我们观察到来自瘦鼠和肥胖鼠的三种 AT 类型（棕色、性腺、腹股沟皮下）的组织特异性和饮食相关差异。棕色 AT 表现出独特的脂质组学特征，具有最大的脂质类别多样性，并通过改变其脂质组成对高脂肪饮食做出反应，使其脂质组成向白色 AT 转变。此外，饮食诱导的肥胖促进了脂质组的整体重塑，三种 AT 类型的长链和多不饱和三酰甘油和磷脂种类都显著增加。
本文提出的方法促进了 AT 可重复的系统脂质组学分析，并且可以与（临床前）研究中使用的其他组学方法相结合，以深入了解肥胖相关疾病发病机制中涉及的分子代谢动态。
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