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Metabolomics reveal mitochondrial and fatty acid metabolism disorders contribute to the development of DKD in T2DM patients

Abstract

Diabetic kidney disease (DKD) is the leading cause of ESRD, while early intervention shows great benefit to prevent the progression of DKD, so sensitive biomarkers for DKD are still desired. This study aims to identify potential biomarkers and reveal underlying pathways in DKD patients by metabolomics. Gas chromatography-mass spectrometry was used to analyze urine obtained from the control, type 2 diabetes mellitus (T2DM) and DKD patients, and the renal histological changes in DKD patients was also assessed. DKD group showed increased level of uric acid, 1,5-Anhydroglucitol, hippuric acid, stearic acid and palmitic acid, and reduced level of uracil, glycine, aconitic acid, isocitric acid, 4-hydroxybutyrate, 2-deoxyerythritol and glycolic acid compared to the control and T2DM groups. Further analysis indicated that many of the changed metabolites were involved in mitochondrial and fatty acids (FA) metabolism, and combined mitochondrial and FA metabolites showed better diagnosis values for DKD. Histological results confirmed that renal expression of key proteins was reduced in DKD patients regarding to mitochondrial biogenesis (PGC-1α, p-AMPK) and FA oxidation (PPAR-α, CPT-1) compared to the control and T2DM. This study highlights that metabolomics is a promising tool to identify biomarkers for DKD, and it also reveals that mitochondrial dysfunction and deficient FA oxidation contribute to the development of DKD.

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Publication details

The article was received on 20 Mar 2017, accepted on 13 Sep 2017 and first published on 14 Sep 2017


Article type: Paper
DOI: 10.1039/C7MB00167C
Citation: Mol. BioSyst., 2017, Accepted Manuscript
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    Metabolomics reveal mitochondrial and fatty acid metabolism disorders contribute to the development of DKD in T2DM patients

    L. Li, C. Wang, H. Yang, S. Liu, Y. Lu, P. Fu and J. Liu, Mol. BioSyst., 2017, Accepted Manuscript , DOI: 10.1039/C7MB00167C

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