Spatial-resolved metabolomics reveals tissue-specific metabolic reprogramming in diabetic nephropathy by using mass spectrometry imaging.
IF: 14.903
Cited by: 34


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.


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


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

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