Comprehensive Analysis of Acylcarnitine Species in db/db Mouse Using a Novel Method of High-Resolution Parallel Reaction Monitoring Reveals Widespread Metabolic Dysfunction Induced by Diabetes,Analytical Chemistry

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Comprehensive Analysis of Acylcarnitine Species in db/db Mouse Using a Novel Method of High-Resolution Parallel Reaction Monitoring Reveals Widespread Metabolic Dysfunction Induced by Diabetes
Analytical Chemistry ( IF 6.7 ) Pub Date : 2017-09-12 00:00:00 , DOI: 10.1021/acs.analchem.7b02283
Li Xiang ₁ , Juntong Wei ₁ , Xiao Yu Tian ₂ , Bei Wang ₁ , Wan Chan ₁ , Shangfu Li ₁ , Zhi Tang ₁ , Hongsong Zhang ₂ , Wai San Cheang ₂ , Qian Zhao ₁ , Hongzhi Zhao ₁ , Zhiyi Yang ₁ , Yanjun Hong ₁ , Yu Huang ₂ , Zongwei Cai ₁

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Acylcarnitines are exerting a variety of biological functions depending on the differences in lengths, saturation levels, and conjugation groups, which to a great extent contribute to the challenges of acylcarnitines quantifications due to various kinds of isomers. Here, we describe a novel method by using high-resolution parallel reaction monitoring (PRM) liquid chromatography-tandem mass spectrometry (LC-MS/MS). Both reversed-phase and normal-phase column were used in order to get accurate, reliable, widespread quantification of acylcarnitines, and without tedious sample preparation procedure. The method provided the most comprehensive acylcarnitine profile with high-resolution MS and MS/MS confirmation to date. A total of 117 acylcarnitines were detected from plasma and urine samples. The application of targeted profiling of acylcarnitines in db/m+ control and db/db diabetic mice indicated incomplete amino acid and fatty acid oxidation on diabetic mice. Interestingly, the reduction of medium odd-numbered chain acylcarnitines in urine samples was first observed between db/m+ and db/db mice. The high-resolution PRM method makes it possible to monitor the widespread metabolic changes of the acylcarnitines in response to stimuli. Besides, the accurate MS and MS/MS spectra data of the 117 acylcarnitines could be used as mass spectrometric resources for the identification of acylcarnitines.

中文翻译：

使用高分辨率的并行反应监测新方法对db / db小鼠中的酰基肉碱物种进行综合分析，揭示了糖尿病引起的广泛代谢功能障碍

酰基肉碱正在发挥各种生物学功能，具体取决于长度，饱和度和共轭基团的差异，这在很大程度上归因于各种异构体对酰基肉碱定量的挑战。在这里，我们描述了一种通过使用高分辨率并行反应监测（PRM）液相色谱-串联质谱（LC-MS / MS）的新方法。为了获得准确，可靠，广泛的酰基肉碱定量分析，无需使用繁琐的样品制备程序，可使用反相和正相色谱柱。该方法提供了迄今为止最全面的酰基肉碱概况，并且具有高分辨率的MS和MS / MS确认信息。从血浆和尿液样品中总共检测到117种酰基肉碱。酰基肉碱的靶向分析在中的应用db / m +对照和db / db糖尿病小鼠表明糖尿病小鼠的氨基酸和脂肪酸氧化不完全。有趣的是，首先在db / m +和db / db小鼠之间观察到尿液样品中中等奇数链酰基肉碱的减少。高分辨率PRM方法使监测肉碱对刺激的广泛代谢变化成为可能。此外，117种酰基肉碱的准确的MS和MS / MS光谱数据可作为鉴定酰基肉碱的质谱资源。

更新日期：2017-09-12

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