美国威斯康星大学麦迪逊分校李灵军团队报道了，使用串联质谱的磷脂和硫酸糖脂的重氮丁酮辅助等压标记实现多重定量脂组学。相关研究成果于2024年2月16日发表于国际顶尖学术期刊《自然—化学》。

基于质谱的定量脂质组学是旨在揭示脂质组学与疾病发展之间的复杂关系的一个新兴领域。然而，由于脂质结构的多样性，以高通量的方式全面量化脂质球蛋白仍然具有挑战性。

该文中，研究人员提出了一种重氮丁酮辅助的等压标记策略作为一种快速而强大的平台，用在广泛的脂质类别（包括各种磷脂和糖脂）中进行多重定量脂质组学。重氮丁酮试剂与磷酸二酯或硫酸酯基团偶联，同时容纳不同脂质类别上的各种官能团，从而能够进行随后的等压标记以进行高通量多重定量。

该方法在标记效率、检测灵敏度、定量准确性和对各种生物样品的广泛适用性方面表现出优异的性能。最后，研究人员对来自瘦和肥胖小鼠肝脏的脂质提取物进行了六重量化分析。总的来说，研究人员以高通量的方式鉴定和量化了246种磷脂，揭示了可能与小鼠肥胖相关的脂质组学变化。

附：英文原文

Title: Diazobutanone-assisted isobaric labelling of phospholipids and sulfated glycolipids enables multiplexed quantitative lipidomics using tandem mass spectrometry

Author: Gu, Ting-Jia, Liu, Peng-Kai, Wang, Yen-Wen, Flowers, Matthew T., Xu, Shuling, Liu, Yuan, Davis, Dawn B., Li, Lingjun

Issue&Volume: 2024-02-16

Abstract: Mass spectrometry-based quantitative lipidomics is an emerging field aiming to uncover the intricate relationships between lipidomes and disease development. However, quantifying lipidomes comprehensively in a high-throughput manner remains challenging owing to the diverse lipid structures. Here we propose a diazobutanone-assisted isobaric labelling strategy as a rapid and robust platform for multiplexed quantitative lipidomics across a broad range of lipid classes, including various phospholipids and glycolipids. The diazobutanone reagent is designed to conjugate with phosphodiester or sulfate groups, while accommodating various functional groups on different lipid classes, enabling subsequent isobaric labelling for high-throughput multiplexed quantitation. Our method demonstrates excellent performance in terms of labelling efficiency, detection sensitivity, quantitative accuracy and broad applicability to various biological samples. Finally, we performed a six-plex quantification analysis of lipid extracts from lean and obese mouse livers. In total, we identified and quantified 246 phospholipids in a high-throughput manner, revealing lipidomic changes that may be associated with obesity in mice.

DOI: 10.1038/s41557-023-01436-2

Source: https://www.nature.com/articles/s41557-023-01436-2