TY - JOUR
T1 - Urinary metabolomic profiling in streptozotocin-induced diabetic mice after treatment with losartan
AU - Hyeon, Jin Seong
AU - Jung, Youngae
AU - Lee, Gayoung
AU - Ha, Hunjoo
AU - Hwang, Geum Sook
N1 - Funding Information:
This study was supported by the National Research Foundation (NRF) grant funded by the Korean Government (NRF-2017M3A9D5A01052449, NRF-2019R1A2C2002720) and Korea Basic Science Institute (C060200).
Funding Information:
Funding: This study was supported by the National Research Foundation (NRF) grant funded by the Korean Government (NRF-2017M3A9D5A01052449, NRF-2019R1A2C2002720) and Korea Basic Science Institute (C060200).
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/12/1
Y1 - 2020/12/1
N2 - Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease and end-stage kidney disease. Renin–angiotensin system inhibitors such as losartan are the predominant therapeutic options in clinical practice to treat DKD. Therefore, it is necessary to identify DKD-related metabolic profiles that are affected by losartan. To investigate the change in metabolism associated with the development of DKD, we performed global and targeted metabolic profiling using 800 MHz nuclear magnetic resonance spectroscopy of urine samples from streptozotocin-induced diabetic mice (DM) with or without losartan administration. A principal component analysis plot showed that the metabolic pattern in the losartan-treated diabetic mice returned from that in the DM group toward that in the control mice (CM). We found that 33 urinary metabolites were significantly changed in DM compared with CM, and the levels of 16 metabolites among them, namely, glucose, mannose, myo-inositol, pyruvate, fumarate, 2-hydroxyglutarate, isobutyrate, glycine, threonine, dimethylglycine, methyldantoin, isoleucine, leucine, acetylcarnitine, 3-hydroxy-3-methylglutarate, and taurine, shifted closer to the control level in response to losartan treatment. Pathway analysis revealed that these metabolites were associated with branched-chain amino acid degradation; taurine and hypotaurine metabolism; glycine, serine, and threonine metabolism; the tricarboxylic acid cycle; and galactose metabolism. Our results demonstrate that metabolomic analysis is a useful tool for identifying the metabolic pathways related to the development of DKD affected by losartan administration and may contribute to the discovery of new therapeutic agents for DKD.
AB - Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease and end-stage kidney disease. Renin–angiotensin system inhibitors such as losartan are the predominant therapeutic options in clinical practice to treat DKD. Therefore, it is necessary to identify DKD-related metabolic profiles that are affected by losartan. To investigate the change in metabolism associated with the development of DKD, we performed global and targeted metabolic profiling using 800 MHz nuclear magnetic resonance spectroscopy of urine samples from streptozotocin-induced diabetic mice (DM) with or without losartan administration. A principal component analysis plot showed that the metabolic pattern in the losartan-treated diabetic mice returned from that in the DM group toward that in the control mice (CM). We found that 33 urinary metabolites were significantly changed in DM compared with CM, and the levels of 16 metabolites among them, namely, glucose, mannose, myo-inositol, pyruvate, fumarate, 2-hydroxyglutarate, isobutyrate, glycine, threonine, dimethylglycine, methyldantoin, isoleucine, leucine, acetylcarnitine, 3-hydroxy-3-methylglutarate, and taurine, shifted closer to the control level in response to losartan treatment. Pathway analysis revealed that these metabolites were associated with branched-chain amino acid degradation; taurine and hypotaurine metabolism; glycine, serine, and threonine metabolism; the tricarboxylic acid cycle; and galactose metabolism. Our results demonstrate that metabolomic analysis is a useful tool for identifying the metabolic pathways related to the development of DKD affected by losartan administration and may contribute to the discovery of new therapeutic agents for DKD.
KW - Diabetic kidney disease
KW - Losartan
KW - Metabolomics
KW - NMR
UR - http://www.scopus.com/inward/record.url?scp=85096806060&partnerID=8YFLogxK
U2 - 10.3390/ijms21238969
DO - 10.3390/ijms21238969
M3 - Article
C2 - 33255934
AN - SCOPUS:85096806060
SN - 1661-6596
VL - 21
SP - 1
EP - 11
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 23
M1 - 8969
ER -