title: Metabonomic analysis of potential biomarkers and drug targets involved in diabetic nephropathy mice.
abstract: Diabetic nephropathy (DN) is one of the lethal manifestations of diabetic systemic microvascular disease. Elucidation of characteristic metabolic alterations during diabetic progression is critical to understand its pathogenesis and identify potential biomarkers and drug targets involved in the disease. In this study, (1)H nuclear magnetic resonance ((1)H NMR)-based metabonomics with correlative analysis was performed to study the characteristic metabolites, as well as the related pathways in urine and kidney samples of db/db diabetic mice, compared with age-matched wildtype mice. The time trajectory plot of db/db mice revealed alterations, in an age-dependent manner, in urinary metabolic profiles along with progression of renal damage and dysfunction. Age-dependent and correlated metabolite analysis identified that cis-aconitate and allantoin could serve as biomarkers for the diagnosis of DN. Further correlative analysis revealed that the enzymes dimethylarginine dimethylaminohydrolase (DDAH), guanosine triphosphate cyclohydrolase I (GTPCH I), and 3-hydroxy-3-methylglutaryl-CoA lyase (HMG-CoA lyase) were involved in dimethylamine metabolism, ketogenesis and GTP metabolism pathways, respectively, and could be potential therapeutic targets for DN. Our results highlight that metabonomic analysis can be used as a tool to identify potential biomarkers and novel therapeutic targets to gain a better understanding of the mechanisms underlying the initiation and progression of diseases.
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035 China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Wei
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035 China.
authors.forename: Liangcai
authors.initials: L
authors.lastname: Zhao
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035 China.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Jia
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035 China.
authors.forename: Huanhuan
authors.initials: H
authors.lastname: Xia
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035 China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Du
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035 China.
authors.forename: Qiuting
authors.initials: Q
authors.lastname: Lin
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035 China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Lin
authors.affiliation: Radiology Department of the Second Affiliated Hospital, Wenzhou Medical University, Wenzhou 325027, China.
authors.forename: Xinjian
authors.initials: X
authors.lastname: Ye
authors.affiliation: Radiology Department of the Second Affiliated Hospital, Wenzhou Medical University, Wenzhou 325027, China.
authors.forename: Zhihan
authors.initials: Z
authors.lastname: Yan
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035 China.
authors.forename: Hongchang
authors.initials: H
authors.lastname: Gao
mesh_terms: D000156:Aconitic Acid / Q000652:urine; D000214:Acyl Coenzyme A / Q000378:metabolism; D000481:Allantoin / Q000652:urine; D000581:Amidohydrolases / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism / Q000652:urine*; D003928:Diabetic Nephropathies / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D016002:Discriminant Analysis; D005227:Fatty Acids / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008297:Male; D055432:Metabolomics; D008744:Methylamines / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008820:Mice, Obese; D019906:Nuclear Magnetic Resonance, Biomolecular; D025341:Principal Component Analysis; D054411:Receptors, Leptin / Q000172:deficiency / Q000235:genetics
chemical_list: D000214:Acyl Coenzyme A; D015415:Biomarkers; D005227:Fatty Acids; D008744:Methylamines; D054411:Receptors, Leptin; C008047:3-hydroxy-3-methylglutaryl-coenzyme A; D000481:Allantoin; D006160:Guanosine Triphosphate; D000156:Aconitic Acid; C027451:methylamine; D000581:Amidohydrolases; C059999:dimethylargininase