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1. Spatial-resolved metabolomics reveals tissue-specific metabolic reprogramming in diabetic nephropathy by using mass spectrometry imaging

Author

Zhonghua Wang, Wenqing Fu, Meiling Huo, Bingshu He, Yaqi Liu, Lu Tian, Wanfang Li, Zhi Zhou, Baili Wang, Jianzhen Xia, Yanhua Chen, Jinfeng Wei, and Zeper Abliz

Subjects
Spatial-resolved metabolomics, Mass spectrometry imaging, Diabetic nephropathy, Metabolic reprogramming, Astragaloside IV, Therapeutics. Pharmacology, RM1-950
Abstract

Detailed knowledge on tissue-specific metabolic reprogramming in diabetic nephropathy (DN) is vital for more accurate understanding the molecular pathological signature and developing novel therapeutic strategies. In the present study, a spatial-resolved metabolomics approach based on air flow-assisted desorption electrospray ionization (AFADESI) and matrix-assisted laser desorption ionization (MALDI) integrated mass spectrometry imaging (MSI) was proposed to investigate tissue-specific metabolic alterations in the kidneys of high-fat diet-fed and streptozotocin (STZ)-treated DN rats and the therapeutic effect of astragaloside IV, a potential anti-diabetic drug, against DN. As a result, a wide range of functional metabolites including sugars, amino acids, nucleotides and their derivatives, fatty acids, phospholipids, sphingolipids, glycerides, carnitine and its derivatives, vitamins, peptides, and metal ions associated with DN were identified and their unique distribution patterns in the rat kidney were visualized with high chemical specificity and high spatial resolution. These region-specific metabolic disturbances were ameliorated by repeated oral administration of astragaloside IV (100 mg/kg) for 12 weeks. This study provided more comprehensive and detailed information about the tissue-specific metabolic reprogramming and molecular pathological signature in the kidney of diabetic rats. These findings highlighted the promising potential of AFADESI and MALDI integrated MSI based metabolomics approach for application in metabolic kidney diseases.

Published
2021
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3. Spatial-resolved metabolomics reveals tissue-specific metabolic reprogramming in diabetic nephropathy by using mass spectrometry imaging

Author

Lu Tian, Wanfang Li, Jinfeng Wei, Zhi Zhou, Yanhua Chen, Zhonghua Wang, Wenqing Fu, Yaqi Liu, Baili Wang, Bingshu He, Meiling Huo, Jianzhen Xia, and Zeper Abliz

Subjects
BUN, blood urea nitrogen, VIP, variable importance in projection, AGEs, advanced glycation end products, p-AMPK, phosphorylated adenosine monophosphate activated protein kinase, Diabetic nephropathy, PG, phosphatidylglycerol, UMP, uridine monophosphate, PC, phosphatidylcholine, GMP, guanosine monophosphate, 0302 clinical medicine, DM, diabetes mellitus, GSH, glutathione, PA, phosphatidic acid, General Pharmacology, Toxicology and Pharmaceutics, PUFA, polyunsaturated fatty acids, LysoPG, lysophosphatidylglycerol, LysoPC, lysophosphatidylcholine, 0303 health sciences, Kidney, TG, triglyceride, Chemistry, GLU, glucose, Metabolic reprogramming, AFADESI, air flow-assisted desorption electrospray ionization, PS, phosphatidylserine, MSI, mass spectrometry imaging, medicine.anatomical_structure, Biochemistry, 030220 oncology & carcinogenesis, SDH, succinate dehydrogenase, Original Article, SGLTs, sodium-glucose cotransporters, TCHO, total cholesterol, medicine.drug, ATP, adenosine triphosphate, CL, cardiolipin, Spatial-resolved metabolomics, FBG, fasting blood glucose, DESI, desorption electrospray ionization, TCA, tricarboxylic acid, PPP, pentose phosphate pathway, HbA1c, glycosylated hemoglobin, RM1-950, AMPK, adenosine monophosphate activated protein kinase, Astragaloside IV, PE, phosphatidylethanolamine, STZ, streptozotocin, Mass spectrometry imaging, DN, diabetic nephropathy, 03 medical and health sciences, ROS, reactive oxygen species, Metabolomics, ROI, regions of interest, medicine, Carnitine, NMR, nuclear magnetic resonance, DPA, docosapentaenoic acid, 030304 developmental biology, Desorption electrospray ionization, Cre, creatinine, SM, sphingomyelin, medicine.disease, Streptozotocin, ESKD, end-stage kidney disease, Sphingolipid, ADP, adenosine diphosphate, MS, mass spectrometry, AMP, adenosine monophosphate, MALDI, matrix-assisted laser desorption ionization, HPLC, high-performance liquid chromatography, Na-CMC, sodium carboxymethyl cellulose, H&E, hematoxylin and eosin, Therapeutics. Pharmacology, DAG, diacylglycerol, AST, astragaloside IV
Abstract

Detailed knowledge on tissue-specific metabolic reprogramming in diabetic nephropathy (DN) is vital for more accurate understanding the molecular pathological signature and developing novel therapeutic strategies. In the present study, a spatial-resolved metabolomics approach based on air flow-assisted desorption electrospray ionization (AFADESI) and matrix-assisted laser desorption ionization (MALDI) integrated mass spectrometry imaging (MSI) was proposed to investigate tissue-specific metabolic alterations in the kidneys of high-fat diet-fed and streptozotocin (STZ)-treated DN rats and the therapeutic effect of astragaloside IV, a potential anti-diabetic drug, against DN. As a result, a wide range of functional metabolites including sugars, amino acids, nucleotides and their derivatives, fatty acids, phospholipids, sphingolipids, glycerides, carnitine and its derivatives, vitamins, peptides, and metal ions associated with DN were identified and their unique distribution patterns in the rat kidney were visualized with high chemical specificity and high spatial resolution. These region-specific metabolic disturbances were ameliorated by repeated oral administration of astragaloside IV (100 mg/kg) for 12 weeks. This study provided more comprehensive and detailed information about the tissue-specific metabolic reprogramming and molecular pathological signature in the kidney of diabetic rats. These findings highlighted the promising potential of AFADESI and MALDI integrated MSI based metabolomics approach for application in metabolic kidney diseases., Graphical abstract The present study revealed region-specific metabolic reprogramming during diabetic nephropathy (DN) by using air flow-assisted desorption electrospray ionization (AFADESI) and matrix-assisted laser desorption ionization (MALDI) mass spectrometry imaging (MSI).Image 1

Published
2021

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