PMID- 28956034 OWN - NLM STAT- MEDLINE DCOM- 20180606 LR - 20180606 IS - 1742-2051 (Electronic) IS - 1742-2051 (Linking) VI - 13 IP - 11 DP - 2017 Oct 24 TI - Metabolomics reveal mitochondrial and fatty acid metabolism disorders that contribute to the development of DKD in T2DM patients. PG - 2392-2400 LID - 10.1039/c7mb00167c [doi] AB - Diabetic kidney disease (DKD) is the leading cause of ESRD; however, early intervention can greatly prevent the progression of DKD; thus, sensitive biomarkers for DKD are still required. This study was aimed at the identification of potential biomarkers and revelation of underlying pathways in DKD patients by non-targeted metabolomics. Gas chromatography-mass spectrometry was used to analyze urine obtained from the control and type 2 diabetes mellitus (T2DM) and DKD patients, and the renal histological changes in DKD patients were assessed. The 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 as compared to the control and T2DM groups. Further analysis indicated that many of the changed metabolites were involved in mitochondrial and fatty acid (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 with respect to mitochondrial biogenesis (PGC-1alpha, p-AMPK) and FA oxidation (PPAR-alpha, CPT-1) as compared to that in the control and T2DM groups. This study highlighted that both mitochondrial and FA metabolism were disturbed in DKD, and thus, they could serve as combined biomarkers for the prediction of DKD. FAU - Li, Ling AU - Li L AD - Kidney Research Institute, Division of Nephrology, West China Hospital of Sichuan University, Chengdu, China. fupinghx@163.com. FAU - Wang, Chengshi AU - Wang C FAU - Yang, Hongliu AU - Yang H FAU - Liu, Shuyun AU - Liu S FAU - Lu, Yanrong AU - Lu Y FAU - Fu, Ping AU - Fu P FAU - Liu, Jingping AU - Liu J LA - eng PT - Journal Article PL - England TA - Mol Biosyst JT - Molecular bioSystems JID - 101251620 RN - 0 (Biomarkers) RN - 0 (Fatty Acids) SB - IM MH - Adult MH - Aged MH - Biomarkers MH - Diabetes Mellitus, Type 2/*etiology/metabolism/pathology MH - Diabetic Nephropathies/*etiology/metabolism/pathology MH - Fatty Acids/*metabolism MH - Female MH - Humans MH - Male MH - Metabolic Diseases/*complications/*metabolism MH - *Metabolomics/methods MH - Middle Aged MH - Mitochondrial Diseases/*complications/*metabolism MH - ROC Curve EDAT- 2017/09/29 06:00 MHDA- 2018/06/07 06:00 CRDT- 2017/09/29 06:00 PHST- 2017/09/29 06:00 [pubmed] PHST- 2018/06/07 06:00 [medline] PHST- 2017/09/29 06:00 [entrez] AID - 10.1039/c7mb00167c [doi] PST - ppublish SO - Mol Biosyst. 2017 Oct 24;13(11):2392-2400. doi: 10.1039/c7mb00167c.