Tissue-Specific <sup>1</sup>H-NMR Metabolomic Profiling in Mice with Adenine-Induced Chronic Kidney Disease
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 <sup>1</sup>H nuclear magnetic resonance (NMR)-based metabolomics profiling of tissues from mice with CKD....
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| Format: | Article |
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MDPI AG
2021-01-01
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| Series: | Metabolites |
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| Online Access: | https://www.mdpi.com/2218-1989/11/1/45 |
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| author | Ram B. Khattri Trace Thome Terence E. Ryan |
| author_facet | Ram B. Khattri Trace Thome Terence E. Ryan |
| author_sort | Ram B. Khattri |
| collection | DOAJ |
| description | 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 <sup>1</sup>H 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, <i>p</i> < 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<sup>+</sup>, 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. |
| first_indexed | 2024-03-09T05:21:07Z |
| format | Article |
| id | doaj.art-50c48f1faf3741ee99e4edeacac04cd0 |
| institution | Directory Open Access Journal |
| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-03-09T05:21:07Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Metabolites |
| spelling | doaj.art-50c48f1faf3741ee99e4edeacac04cd02023-12-03T12:40:12ZengMDPI AGMetabolites2218-19892021-01-011114510.3390/metabo11010045Tissue-Specific <sup>1</sup>H-NMR Metabolomic Profiling in Mice with Adenine-Induced Chronic Kidney DiseaseRam B. Khattri0Trace Thome1Terence E. Ryan2Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL 32611, USADepartment of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL 32611, USADepartment of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL 32611, USAChronic 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 <sup>1</sup>H 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, <i>p</i> < 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<sup>+</sup>, 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.https://www.mdpi.com/2218-1989/11/1/45CKDuremiametabolismmusclecardiacliver |
| spellingShingle | Ram B. Khattri Trace Thome Terence E. Ryan Tissue-Specific <sup>1</sup>H-NMR Metabolomic Profiling in Mice with Adenine-Induced Chronic Kidney Disease Metabolites CKD uremia metabolism muscle cardiac liver |
| title | Tissue-Specific <sup>1</sup>H-NMR Metabolomic Profiling in Mice with Adenine-Induced Chronic Kidney Disease |
| title_full | Tissue-Specific <sup>1</sup>H-NMR Metabolomic Profiling in Mice with Adenine-Induced Chronic Kidney Disease |
| title_fullStr | Tissue-Specific <sup>1</sup>H-NMR Metabolomic Profiling in Mice with Adenine-Induced Chronic Kidney Disease |
| title_full_unstemmed | Tissue-Specific <sup>1</sup>H-NMR Metabolomic Profiling in Mice with Adenine-Induced Chronic Kidney Disease |
| title_short | Tissue-Specific <sup>1</sup>H-NMR Metabolomic Profiling in Mice with Adenine-Induced Chronic Kidney Disease |
| title_sort | tissue specific sup 1 sup h nmr metabolomic profiling in mice with adenine induced chronic kidney disease |
| topic | CKD uremia metabolism muscle cardiac liver |
| url | https://www.mdpi.com/2218-1989/11/1/45 |
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