INTRODUCTION Diabetic kidney disease (DKD) is the most prevalent complication in diabetic patients, which contributes to high morbidity and mortality. Urine and plasma metabolomics studies have been demonstrated to provide valuable insights for DKD. However, limited information on spatial distributions of metabolites in kidney tissues have been reported. OBJECTIVES In this work, we employed an ambient desorption electrospray ionization-mass spectrometry imaging (DESI-MSI) coupled to a novel bioinformatics platform (METASPACE) to characterize the metabolome in a mouse model of DKD. METHODS DESI-MSI was performed for spatial untargeted metabolomics analysis in kidneys of mouse models (F1 C57BL/6J-Ins2Akita male mice at 17 weeks of age) of type 1 diabetes (T1D, n = 5) and heathy controls (n = 6). RESULTS Multivariate analyses (i.e., PCA and PLS-DA (a 2000 permutation test: P < 0.001)) showed clearly separated clusters for the two groups of mice on the basis of 878 measured m/z's in kidney cortical tissues. Specifically, mice with T1D had increased relative abundances of pseudouridine, accumulation of free polyunsaturated fatty acids (PUFAs), and decreased relative abundances of cardiolipins in cortical proximal tubules when compared with healthy controls. CONCLUSION Results from the current study support potential key roles of pseudouridine and cardiolipins for maintaining normal RNA structure and normal mitochondrial function, respectively, in cortical proximal tubules with DKD. DESI-MSI technology coupled with METASPACE could serve as powerful new tools to provide insight on fundamental pathways in DKD.

中文翻译：

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DESI-MSI 和 METASPACE 表明糖尿病肾近曲小管中的脂质异常和线粒体膜成分改变。


简介 糖尿病肾病（DKD）是糖尿病患者最常见的并发症，导致高发病率和死亡率。尿液和血浆代谢组学研究已被证明可为 DKD 提供有价值的见解。然而，有关肾组织代谢物空间分布的信息有限。目的 在这项工作中，我们采用常温解吸电喷雾电离质谱成像 (DESI-MSI) 与新型生物信息学平台 (METASPACE) 相结合来表征 DKD 小鼠模型的代谢组。方法 对 1 型糖尿病 (T1D，n = 5) 和健康对照 (n = 6) 小鼠模型（17 周龄的 F1 C57BL/6J-Ins2Akita 雄性小鼠）和健康对照小鼠模型（n = 6）的肾脏进行 DESI-MSI 进行空间非靶向代谢组学分析。结果 多变量分析（即 PCA 和 PLS-DA（2000 年排列检验：P < 0.001））显示，基于肾皮质组织中 878 个测量的 m/z，两组小鼠的簇明显分开。具体而言，与健康对照组相比，患有 T1D 的小鼠的假尿苷相对丰度增加，游离多不饱和脂肪酸 (PUFA) 积累，并且皮质近端小管中心磷脂的相对丰度降低。结论 目前的研究结果支持假尿苷和心磷脂在 DKD 皮质近曲小管中分别维持正常 RNA 结构和正常线粒体功能的潜在关键作用。 DESI-MSI 技术与 METASPACE 相结合可以作为强大的新工具来提供对 DKD 基本途径的洞察。