title: GC/TOFMS analysis of metabolites in serum and urine reveals metabolic perturbation of TCA cycle in db/db mice involved in diabetic nephropathy.
abstract: Early diagnosis of diabetic nephropathy (DN) is difficult although it is of crucial importance to prevent its development. To probe potential markers and the underlying mechanism of DN, an animal model of DN, the db/db mice, was used and serum and urine metabolites were profiled using gas chromatography/time-of-flight mass spectrometry. Metabolic patterns were evaluated based on serum and urine data. Principal component analysis of the data revealed an obvious metabonomic difference between db/db mice and controls, and db/db mice showed distinctly different metabolic patterns during the progression from diabetes to early, medium, and later DN. The identified metabolites discriminating between db/db mice and controls suggested that db/db mice have perturbations in the tricarboxylic acid cycle (TCA, citrate, malate, succinate, and aconitate), lipid metabolism, glycolysis, and amino acid turnover. The db/db mice were characterized by acidic urine, high TCA intermediates in serum at week 6 and a sharp decline thereafter, and gradual elevation of free fatty acids in the serum. The sharp drop of serum TCA intermediates from week 6 to 8 indicated the downregulated glycolysis and insulin resistance. However, urinary TCA intermediates did not decrease in parallel with those in the serum from week 6 to 10, and an increased portion of TCA intermediates in the serum was excreted into the urine at 8, 10, and 12 wk than at 6 wk, indicating kidney dysfunction occurred. The relative abundances of TCA intermediates in urine relative to those in serum were suggested as an index of renal damage.
authors: Laboratory of Metabolomics, Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.
authors: Mengjie
authors: M
authors: Li
authors: Xufang
authors: X
authors: Wang
authors: Jiye
authors: J
authors: Aa
authors: Weisong
authors: W
authors: Qin
authors: Weibin
authors: W
authors: Zha
authors: Yongchun
authors: Y
authors: Ge
authors: Linsheng
authors: L
authors: Liu
authors: Tian
authors: T
authors: Zheng
authors: Bei
authors: B
authors: Cao
authors: Jian
authors: J
authors: Shi
authors: Chunyan
authors: C
authors: Zhao
authors: Xinwen
authors: X
authors: Wang
authors: Xiaoyi
authors: X
authors: Yu
authors: Guangji
authors: G
authors: Wang
authors: Zhihong
authors: Z
authors: Liu
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000097:blood / Q000652:urine; D000419:Albuminuria / Q000652:urine; D000481:Allantoin / Q000652:urine; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid / Q000097:blood; D015415:Biomarkers; D002784:Cholesterol / Q000097:blood; D019343:Citric Acid / Q000097:blood; D002952:Citric Acid Cycle / Q000502:physiology*; D003928:Diabetic Nephropathies / Q000097:blood* / Q000652:urine*; D008401:Gas Chromatography-Mass Spectrometry; D006019:Glycolysis; D006863:Hydrogen-Ion Concentration; D050356:Lipid Metabolism; D008239:Lysine / Q000097:blood; D008293:Malates / Q000652:urine; D008297:Male; D055432:Metabolomics; D051379:Mice; D008810:Mice, Inbred C57BL; D019802:Succinic Acid / Q000652:urine; D014556:Urine
chemical_list: D000596:Amino Acids; D015415:Biomarkers; D008293:Malates; D016718:Arachidonic Acid; D019343:Citric Acid; D000481:Allantoin; C030298:malic acid; D002784:Cholesterol; D019802:Succinic Acid; D008239:Lysine; D020155:3-Hydroxybutyric Acid
keywords: diabetic nephropathy; gas chromatography mass spectrometry; metabonomics; tricarboxylic acid cycle