Chronic kidney disease (CKD) results in the impaired filtration of metabolites, which may be toxic or harmful to organs/tissues. The objective of this study was to perform unbiased ¹H nuclear magnetic resonance (NMR)-based metabolomics profiling of tissues from mice with CKD. Five-month-old male C57BL6J mice were placed on either a casein control diet or adenine-supplemented diet to induce CKD for 24 weeks. CKD was confirmed by significant increases in blood urea nitrogen (24.1 ± 7.7 vs. 105.3 ± 18.3 mg/dL, p < 0.0001) in adenine-fed mice. Following this chronic adenine diet, the kidney, heart, liver, and quadriceps muscles were rapidly dissected; snap-frozen in liquid nitrogen; and the metabolites were extracted. Metabolomic profiling coupled with multivariate analyses confirm clear separation in both aqueous and organic phases between control and CKD mice. Severe energetic stress and apparent impaired mitochondrial metabolism were observed in CKD kidneys evidenced by the depletion of ATP and NAD⁺, along with significant alterations in tricarboxylic acid (TCA) cycle intermediates. Altered amino acid metabolism was observed in all tissues, although significant differences in specific amino acids varied across tissue types. Taken together, this study provides a metabolomics fingerprint of multiple tissues from mice with and without severe CKD induced by chronic adenine feeding.

中文翻译：

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腺嘌呤诱发慢性肾病小鼠的组织特异性 1H-NMR 代谢组学分析


慢性肾脏病（CKD）会导致代谢物过滤受损，这可能对器官/组织有毒或有害。本研究的目的是对 CKD 小鼠的组织进行基于¹ H 核磁共振 (NMR) 的无偏代谢组学分析。 5 个月大的雄性 C57BL6J 小鼠被置于酪蛋白对照饮食或腺嘌呤补充饮食中，以诱导 CKD 24 周。腺嘌呤喂养小鼠的血尿素氮显着增加（24.1 ± 7.7 vs. 105.3 ± 18.3 mg/dL， p < 0.0001）证实了 CKD。在这种长期的腺嘌呤饮食之后，肾脏、心脏、肝脏和股四头肌被迅速解剖；在液氮中速冻；并提取代谢物。代谢组学分析与多变量分析相结合证实了对照小鼠和 CKD 小鼠之间水相和有机相的明显分离。在 CKD 肾脏中观察到严重的能量应激和明显受损的线粒体代谢，表现为 ATP 和 NAD ⁺的消耗，以及三羧酸 (TCA) 循环中间体的显着变化。在所有组织中都观察到氨基酸代谢的改变，尽管特定氨基酸的显着差异因组织类型而异。总而言之，这项研究提供了患有或不患有慢性腺嘌呤喂养诱导的严重 CKD 的小鼠的多个组织的代谢组学指纹。