In situ Metabolomics of Metabolic Reprogramming Involved in a Mouse Model of Type 2 Diabetic Kidney Disease

Linnan, Bai; Yanzhe, Wang; Zhang, Ling; Liu, Yuyuan; Sijia, Chen; Xie, Xiang; Li, Fengqin; Wang, Xiaoxia

doi:10.3389/fphys.2021.779683

Cited by 11 publications

(8 citation statements)

References 59 publications

(79 reference statements)

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“…Although there have been few publications discussing a direct association between unsaturated fatty acids and DKD, low linolenic and linoleic acid intake are associated with CKD in T2DM patients, suggesting an insufficiency of glycerol phospholipid in DKD patients [ 46 ]. In our study, KEGG pathway analysis showed that the unsaturated fatty acids biosynthesis pathway was significantly affected, similar to the metabolic reprogramming observed in a mouse model of DKD [ 26 ].…”

Section: Discussionsupporting

confidence: 77%

“…In a mouse model of DKD, Bai Linnan et al. used situ metabolomics to show perturbation in arginine and proline metabolism [ 26 ]. An earlier study showed that plasma levels of amino acids such as proline, ornithine, and citrulline, were significantly elevated in uremic patients before dialysis, compared with controls, indicating abnormalities in amino acid metabolism, especially proline metabolism [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

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Extracellular vesicles metabolic changes reveals plasma signature in stage-dependent diabetic kidney disease

et al. 2022

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Objective Early diagnosis of diabetic kidney disease (DKD) has long been a complex problem. This study aimed to analyze the metabolomic characteristics of plasma extracellular vesicles (EVs) at different stages of DKD in order to evaluate the metabolites of plasma EVs and select new biomarkers for the early diagnosis of DKD. Patients and methods A total of 78 plasma samples were collected, including samples from 20 healthy controls, 20 patients with type 2 diabetes mellitus (T2DM), 18 patients with DKD stage III, and 20 patients with DKD stage IV. In addition, EVs were isolated for metabolomics analysis. Results The results identified differences in EV metabolomic characteristics in DKD patients at different stages, as well as significant differences in EV metabolomics between T2DM patients without DKD and patients with DKD. Ten Significantly differential metabolites were associated with the occurrence and progression of DKD. Uracil, LPC(O-18:1/0:0), sphingosine 1-phosphate, and 4-acetamidobutyric acid were identified as potential early biomarkers for DKD, showing excellent predictive performance. Conclusion Uracil, LPC(O-18:1/0:0), sphingosine 1-phosphate, and 4-acetamidobutyric acid exhibited potential as suitable biomarkers for early DKD diagnosis. Unexpectedly, combining these four candidate metabolites resulted in enhanced predictive ability for DKD.

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Section: Discussionsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Extracellular vesicles metabolic changes reveals plasma signature in stage-dependent diabetic kidney disease

et al. 2022

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“…The fan charts ( Figure 4 C,D) depict the proportion of differential metabolites found in the different regions of the kidney. The analysis revealed that the ranking of the number of discriminating metabolites identified in the different regions of the HFD/STZ-induced rat kidneys was OM/C > W > IM, while in the db/db mice, the ranking was OM > W > C > IM, indicating that the outer medulla region may be more vulnerable to diabetic renal damage in comparison to the other regions [ 21 , 22 ].…”

Section: Resultsmentioning

confidence: 99%

Comparison of Local Metabolic Changes in Diabetic Rodent Kidneys Using Mass Spectrometry Imaging

et al. 2023

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Understanding the renal region-specific metabolic alteration in different animal models of diabetic nephropathy (DN) is critical for uncovering the underlying mechanisms and for developing effective treatments. In the present study, spatially resolved metabolomics based on air flow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI) was used to compare the local metabolic changes in the kidneys of HFD/STZ-induced diabetic rats and db/db mice. As a result, a total of 67 and 59 discriminating metabolites were identified and visualized in the kidneys of the HFD/STZ-induced diabetic rats and db/db mice, respectively. The result showed that there were significant region-specific changes in the glycolysis, TCA cycle, lipid metabolism, carnitine metabolism, choline metabolism, and purine metabolism in both DN models. However, the regional levels of the ten metabolites, including glucose, AMP, eicosenoic acid, eicosapentaenoic acid, Phosphatidylserine (36:1), Phosphatidylserine (36:4), Phosphatidylethanolamine (34:1), Phosphatidylethanolamine (36:4), Phosphatidylcholine (34:2), Phosphatidylinositol (38:5) were changed in reversed directions, indicating significant differences in the local metabolic phenotypes of these two commonly used DN animal models. This study provides comprehensive and in-depth analysis of the differences in the tissue and molecular pathological features in diabetic kidney injury in HFD/STZ-induced diabetic rats and db/db mice.

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“…Therefore, the importance is evident to investigate molecular changes in nephron segments besides the glomerulus. Others have applied MALDI-MSI to investigate molecular changes of the kidney in animal models of early diabetes and DN [13][14][15][16][17][18] . These studies all revealed changes in renal metabolism upon diabetes, with differences in response between the cortical and medullary regions.…”

Section: Openmentioning

confidence: 99%

Phosphatidylinositol metabolism of the renal proximal tubule S3 segment is disturbed in response to diabetes

Rietjens

Wang

Velden

et al. 2023

Sci Rep

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Diabetes is a main risk factor for kidney disease, causing diabetic nephropathy in close to half of all patients with diabetes. Metabolism has recently been identified to be decisive in cell fate decisions and repair. Here we used mass spectrometry imaging (MSI) to identify tissue specific metabolic dysregulation, in order to better understand early diabetes-induced metabolic changes of renal cell types. In our experimental diabetes mouse model, early glomerular glycocalyx barrier loss and systemic metabolic changes were observed. In addition, MSI targeted at small molecule metabolites and glycero(phospho)lipids exposed distinct changes upon diabetes in downstream nephron segments. Interestingly, the outer stripe of the outer medullar proximal tubular segment (PT_S3) demonstrated the most distinct response compared to other segments. Furthermore, phosphatidylinositol lipid metabolism was altered specifically in PT_S3, with one of the phosphatidylinositol fatty acid tails being exchanged from longer unsaturated fatty acids to shorter, more saturated fatty acids. In acute kidney injury, the PT_S3 segment and its metabolism are already recognized as important factors in kidney repair processes. The current study exposes early diabetes-induced changes in membrane lipid composition in this PT_S3 segment as a hitherto unrecognized culprit in the early renal response to diabetes.

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In situ Metabolomics of Metabolic Reprogramming Involved in a Mouse Model of Type 2 Diabetic Kidney Disease

Cited by 11 publications

References 59 publications

Extracellular vesicles metabolic changes reveals plasma signature in stage-dependent diabetic kidney disease

Extracellular vesicles metabolic changes reveals plasma signature in stage-dependent diabetic kidney disease

Comparison of Local Metabolic Changes in Diabetic Rodent Kidneys Using Mass Spectrometry Imaging

Phosphatidylinositol metabolism of the renal proximal tubule S3 segment is disturbed in response to diabetes

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