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Metabonomic analysis of potential biomarkers and drug targets involved in diabetic nephropathy mice.

Wei T, Zhao L, Jia J, Xia H, Du Y, Lin Q, Lin X, Ye X, Yan Z, Gao H - Sci Rep (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035 China.

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.

No MeSH data available.


Related in: MedlinePlus

NMR spectra of kidney samples.Representative 1H NMR spectra of kidney samples obtained from the wildtype mice (A) and db/db mice (B), respectively.
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f5: NMR spectra of kidney samples.Representative 1H NMR spectra of kidney samples obtained from the wildtype mice (A) and db/db mice (B), respectively.

Mentions: Representative 1H-NMR spectra and peak assignments of the metabolites of the kidney tissue extracts obtained from 17-week-old db/db mice are shown in Fig. 5. Similar to that of the urinary metabolites, the PLS-DA score plot of the renal tissue samples (Fig. 6A) from the 17-week-old db/db mice and wildtype mice showed clear differences along the PC1 direction. The validation plot of permutation tests showed that the PLS-DA model built for db/db mice and wildtype mice was robust and credible (Fig. 6B). The corresponding loading plot (Fig. 6C) indicated that the variables corresponding to 3-HB, lactate, acetate, glutamate, succinate, creatinine, choline, glycerophosphocholine (GPC), trimetlylamine oxide (TMAO), myo-inositol, glycine, uridine, inosine, fumarate, phenylalaine, and niacinamide were responsible for the separation.


Metabonomic analysis of potential biomarkers and drug targets involved in diabetic nephropathy mice.

Wei T, Zhao L, Jia J, Xia H, Du Y, Lin Q, Lin X, Ye X, Yan Z, Gao H - Sci Rep (2015)

NMR spectra of kidney samples.Representative 1H NMR spectra of kidney samples obtained from the wildtype mice (A) and db/db mice (B), respectively.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4493693&req=5

f5: NMR spectra of kidney samples.Representative 1H NMR spectra of kidney samples obtained from the wildtype mice (A) and db/db mice (B), respectively.
Mentions: Representative 1H-NMR spectra and peak assignments of the metabolites of the kidney tissue extracts obtained from 17-week-old db/db mice are shown in Fig. 5. Similar to that of the urinary metabolites, the PLS-DA score plot of the renal tissue samples (Fig. 6A) from the 17-week-old db/db mice and wildtype mice showed clear differences along the PC1 direction. The validation plot of permutation tests showed that the PLS-DA model built for db/db mice and wildtype mice was robust and credible (Fig. 6B). The corresponding loading plot (Fig. 6C) indicated that the variables corresponding to 3-HB, lactate, acetate, glutamate, succinate, creatinine, choline, glycerophosphocholine (GPC), trimetlylamine oxide (TMAO), myo-inositol, glycine, uridine, inosine, fumarate, phenylalaine, and niacinamide were responsible for the separation.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035 China.

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.

No MeSH data available.


Related in: MedlinePlus