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Metabolomics. 2020 Jan 10;16(1):11. doi: 10.1007/s11306-020-1637-8.

DESI-MSI and METASPACE indicates lipid abnormalities and altered mitochondrial membrane components in diabetic renal proximal tubules.

Author information

1
Center for Renal Precision Medicine, Division of Nephrology, Department of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
2
Audie L. Murphy Memorial VA Hospital, South Texas Veterans Health Care System, San Antonio, TX, USA.
3
Department of Chemistry, The University of Texas at Austin, Austin, TX, USA.
4
Division of Nephrology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
5
Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, WA, USA.
6
Department of Pathology, University of Texas Health San Antonio, San Antonio, TX, USA.
7
Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany.
8
Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA.
9
Center for Renal Precision Medicine, Division of Nephrology, Department of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA. sharmak3@uthscsa.edu.
10
Audie L. Murphy Memorial VA Hospital, South Texas Veterans Health Care System, San Antonio, TX, USA. sharmak3@uthscsa.edu.

Abstract

INTRODUCTION:

Diabetic kidney disease (DKD) is the most prevalent complication in diabetic patients, which contributes to high morbidity and mortality. Urine and plasma metabolomics studies have been demonstrated to provide valuable insights for DKD. However, limited information on spatial distributions of metabolites in kidney tissues have been reported.

OBJECTIVES:

In this work, we employed an ambient desorption electrospray ionization-mass spectrometry imaging (DESI-MSI) coupled to a novel bioinformatics platform (METASPACE) to characterize the metabolome in a mouse model of DKD.

METHODS:

DESI-MSI was performed for spatial untargeted metabolomics analysis in kidneys of mouse models (F1 C57BL/6J-Ins2Akita male mice at 17 weeks of age) of type 1 diabetes (T1D, n = 5) and heathy controls (n = 6).

RESULTS:

Multivariate analyses (i.e., PCA and PLS-DA (a 2000 permutation test: P < 0.001)) showed clearly separated clusters for the two groups of mice on the basis of 878 measured m/z's in kidney cortical tissues. Specifically, mice with T1D had increased relative abundances of pseudouridine, accumulation of free polyunsaturated fatty acids (PUFAs), and decreased relative abundances of cardiolipins in cortical proximal tubules when compared with healthy controls.

CONCLUSION:

Results from the current study support potential key roles of pseudouridine and cardiolipins for maintaining normal RNA structure and normal mitochondrial function, respectively, in cortical proximal tubules with DKD. DESI-MSI technology coupled with METASPACE could serve as powerful new tools to provide insight on fundamental pathways in DKD.

KEYWORDS:

DESI-MSI; Diabetic kidney disease; Lipid metabolism; Renal proximal tubule

PMID:
31925564
DOI:
10.1007/s11306-020-1637-8

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