The metabolic profile of a rat model of chronic kidney disease

Yohei Tanada, Junji Okuda, Takao Kato, Eri Minamino-Muta, Ichijiro Murata, Tomoyoshi Soga, Tetsuo Shioi, Takeshi Kimura

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background. The kidney is always subjected to high metabolic demand. The aim of this study was to characterize metabolic profiles of a rat model of chronic kidney disease (CKD) with cardiorenal syndrome (CRS) induced by prolonged hypertension. Methods. We used inbred male Dahl salt-sensitive (DS) rats fed an 8% NaCl diet from six weeks of age (high-salt; HS group) or a 0.3% NaCl diet as controls (low-salt; LS group). We analyzed function, pathology, metabolome, and the gene expression related to energy metabolism of the kidney. Results. DS rats with a high-salt diet showed hypertension at 11 weeks of age and elevated serum levels of creatinine and blood urea nitrogen with heart failure at 21 weeks of age. The fibrotic area in the kidneys increased at 21 weeks of age. In addition, gene expression related to mitochondrial function was largely decreased. The levels of citrate and isocitrate increased and the gene expression of alpha-ketoglutaratedehydrogenase and succinyl-CoA synthetase decreased; these are enzymes that metabolize citrate and isocitrate, respectively. In addition, the levels of succinate and acetyl Co-A, both of which are metabolites of the tricarboxylic acid (TCA) cycle, decreased. Conclusions. DS rats fed a high-salt diet were deemed a suitable model of CKD with CRS. Gene expression and metabolites related to energy metabolism and mitochondria in the kidney significantly changed in DS rats with hypertension in accordance with the progression of renal injury.

Original languageEnglish
Article number3352
JournalPeerJ
Volume2017
Issue number5
DOIs
Publication statusPublished - 2017

Fingerprint

Metabolome
Inbred Dahl Rats
kidney diseases
Chronic Renal Insufficiency
Rats
Salts
animal models
salts
Kidney
Cardio-Renal Syndrome
Diet
Gene Expression
Nutrition
Gene expression
kidneys
Hypertension
Citric Acid
Energy Metabolism
hypertension
Succinate-CoA Ligases

Keywords

  • Cardiorenal syndrome
  • CKD
  • Hypertension
  • Metabolome
  • Mitochondria
  • Rat models

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Tanada, Y., Okuda, J., Kato, T., Minamino-Muta, E., Murata, I., Soga, T., ... Kimura, T. (2017). The metabolic profile of a rat model of chronic kidney disease. PeerJ, 2017(5), [3352]. https://doi.org/10.7717/peerj.3352

The metabolic profile of a rat model of chronic kidney disease. / Tanada, Yohei; Okuda, Junji; Kato, Takao; Minamino-Muta, Eri; Murata, Ichijiro; Soga, Tomoyoshi; Shioi, Tetsuo; Kimura, Takeshi.

In: PeerJ, Vol. 2017, No. 5, 3352, 2017.

Research output: Contribution to journalArticle

Tanada, Y, Okuda, J, Kato, T, Minamino-Muta, E, Murata, I, Soga, T, Shioi, T & Kimura, T 2017, 'The metabolic profile of a rat model of chronic kidney disease', PeerJ, vol. 2017, no. 5, 3352. https://doi.org/10.7717/peerj.3352
Tanada Y, Okuda J, Kato T, Minamino-Muta E, Murata I, Soga T et al. The metabolic profile of a rat model of chronic kidney disease. PeerJ. 2017;2017(5). 3352. https://doi.org/10.7717/peerj.3352
Tanada, Yohei ; Okuda, Junji ; Kato, Takao ; Minamino-Muta, Eri ; Murata, Ichijiro ; Soga, Tomoyoshi ; Shioi, Tetsuo ; Kimura, Takeshi. / The metabolic profile of a rat model of chronic kidney disease. In: PeerJ. 2017 ; Vol. 2017, No. 5.
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N2 - Background. The kidney is always subjected to high metabolic demand. The aim of this study was to characterize metabolic profiles of a rat model of chronic kidney disease (CKD) with cardiorenal syndrome (CRS) induced by prolonged hypertension. Methods. We used inbred male Dahl salt-sensitive (DS) rats fed an 8% NaCl diet from six weeks of age (high-salt; HS group) or a 0.3% NaCl diet as controls (low-salt; LS group). We analyzed function, pathology, metabolome, and the gene expression related to energy metabolism of the kidney. Results. DS rats with a high-salt diet showed hypertension at 11 weeks of age and elevated serum levels of creatinine and blood urea nitrogen with heart failure at 21 weeks of age. The fibrotic area in the kidneys increased at 21 weeks of age. In addition, gene expression related to mitochondrial function was largely decreased. The levels of citrate and isocitrate increased and the gene expression of alpha-ketoglutaratedehydrogenase and succinyl-CoA synthetase decreased; these are enzymes that metabolize citrate and isocitrate, respectively. In addition, the levels of succinate and acetyl Co-A, both of which are metabolites of the tricarboxylic acid (TCA) cycle, decreased. Conclusions. DS rats fed a high-salt diet were deemed a suitable model of CKD with CRS. Gene expression and metabolites related to energy metabolism and mitochondria in the kidney significantly changed in DS rats with hypertension in accordance with the progression of renal injury.

AB - Background. The kidney is always subjected to high metabolic demand. The aim of this study was to characterize metabolic profiles of a rat model of chronic kidney disease (CKD) with cardiorenal syndrome (CRS) induced by prolonged hypertension. Methods. We used inbred male Dahl salt-sensitive (DS) rats fed an 8% NaCl diet from six weeks of age (high-salt; HS group) or a 0.3% NaCl diet as controls (low-salt; LS group). We analyzed function, pathology, metabolome, and the gene expression related to energy metabolism of the kidney. Results. DS rats with a high-salt diet showed hypertension at 11 weeks of age and elevated serum levels of creatinine and blood urea nitrogen with heart failure at 21 weeks of age. The fibrotic area in the kidneys increased at 21 weeks of age. In addition, gene expression related to mitochondrial function was largely decreased. The levels of citrate and isocitrate increased and the gene expression of alpha-ketoglutaratedehydrogenase and succinyl-CoA synthetase decreased; these are enzymes that metabolize citrate and isocitrate, respectively. In addition, the levels of succinate and acetyl Co-A, both of which are metabolites of the tricarboxylic acid (TCA) cycle, decreased. Conclusions. DS rats fed a high-salt diet were deemed a suitable model of CKD with CRS. Gene expression and metabolites related to energy metabolism and mitochondria in the kidney significantly changed in DS rats with hypertension in accordance with the progression of renal injury.

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