Metabolic changes in urine and serum during progression of diabetic kidney disease in a mouse model

Kim, Nan Hee; Hyeon, Jin Seong; Cho, Ahreum; Lee, Ga-Young; Jang, Seo Young; Kim, Mi Kyung; Lee, Eun Young; Chung, Choon Hee; Ha, Hunjoo; Hwang, Gwi Seo

doi:10.1016/j.abb.2018.03.042

Cited by 12 publications

(10 citation statements)

References 32 publications

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“…Taken together, our 8-week old db/db mice fed with HFD during 5 weeks reflected characteristic changes of early diabetic nephropathy, such as glomerular hyperfiltration and hypertrophy, as evidenced by significantly lower plasma and urinary creatinine levels and higher kidney weight. Moreover, their phenotypic and metabolic data show obesity, hyperglycemia, dyslipidemia, and inflammation, confirming previous reports about insulin resistance and fatty liver (steatosis) in db/db mice of similar age [13,14,[18][19][20]].…”

Section: Analysis Of Creatinine In Eight Murine Tissuessupporting

confidence: 89%

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Validation of Candidate Phospholipid Biomarkers of Chronic Kidney Disease in Hyperglycemic Individuals and Their Organ-Specific Exploration in Leptin Receptor-Deficient db/db Mouse

et al. 2021

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Biological exploration of early biomarkers for chronic kidney disease (CKD) in (pre)diabetic individuals is crucial for personalized management of diabetes. Here, we evaluated two candidate biomarkers of incident CKD (sphingomyelin (SM) C18:1 and phosphatidylcholine diacyl (PC aa) C38:0) concerning kidney function in hyperglycemic participants of the Cooperative Health Research in the Region of Augsburg (KORA) cohort, and in two biofluids and six organs of leptin receptor-deficient (db/db) mice and wild type controls. Higher serum concentrations of SM C18:1 and PC aa C38:0 in hyperglycemic individuals were found to be associated with lower estimated glomerular filtration rate (eGFR) and higher odds of CKD. In db/db mice, both metabolites had a significantly lower concentration in urine and adipose tissue, but higher in the lungs. Additionally, db/db mice had significantly higher SM C18:1 levels in plasma and liver, and PC aa C38:0 in adrenal glands. This cross-sectional human study confirms that SM C18:1 and PC aa C38:0 associate with kidney dysfunction in pre(diabetic) individuals, and the animal study suggests a potential implication of liver, lungs, adrenal glands, and visceral fat in their systemic regulation. Our results support further validation of the two phospholipids as early biomarkers of renal disease in patients with (pre)diabetes.

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Section: Analysis Of Creatinine In Eight Murine Tissuessupporting

confidence: 89%

“…The leptin-receptor deficient mouse model (db/db) was shown to exhibit a very consistent and robust increase in albuminuria and mesangial matrix expansion. It is therefore a well-established model for human diabetic nephropathy [13,14].…”

Section: Introductionmentioning

confidence: 99%

Validation of Candidate Phospholipid Biomarkers of Chronic Kidney Disease in Hyperglycemic Individuals and Their Organ-Specific Exploration in Leptin Receptor-Deficient db/db Mouse

et al. 2021

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“…These results show TCA cycle dysfunction [136]. In contrast, in a mouse model of DN, pyruvate, citrate, α-KGDH, and fumarate are upregulated [137]. Moreover, in UUO, succinate levels increase, attributed to TCA cycle dysfunction [138].…”

Section: Tca Cycle Redox-sensitive Signaling Pathway In Kidney Diseasesmentioning

confidence: 80%

Mitochondrial Redox Signaling and Oxidative Stress in Kidney Diseases

et al. 2021

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Mitochondria are essential organelles in physiology and kidney diseases, because they produce cellular energy required to perform their function. During mitochondrial metabolism, reactive oxygen species (ROS) are produced. ROS function as secondary messengers, inducing redox-sensitive post-translational modifications (PTM) in proteins and activating or deactivating different cell signaling pathways. However, in kidney diseases, ROS overproduction causes oxidative stress (OS), inducing mitochondrial dysfunction and altering its metabolism and dynamics. The latter processes are closely related to changes in the cell redox-sensitive signaling pathways, causing inflammation and apoptosis cell death. Although mitochondrial metabolism, ROS production, and OS have been studied in kidney diseases, the role of redox signaling pathways in mitochondria has not been addressed. This review focuses on altering the metabolism and dynamics of mitochondria through the dysregulation of redox-sensitive signaling pathways in kidney diseases.

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“…Previous studies have demonstrated that the levels of TCA intermediates in the serum of db/db mice showed an elevation at 6 weeks of age but a sharp drop from 8 weeks of age, which indicates that the utilization of glucose via TCA cycles could be inefficient during type 2 diabetes [44]. In addition, elevated levels of intermediates during TCA cycles (fumarate, 2-OG and citrate) and glycolysis (lactate) in the urine and kidney of db/db mice after 8 weeks have also been reported [10, 45, 46]. In our study, reduced levels of intermediates during TCA cycles and glycolysis occurred in the plasma of db/db mice at later stages.…”

Section: Discussionmentioning

confidence: 99%

“…These changes finally lead to glomerular filtration barrier damage and mesangial and tubulointerstitial expansion or hypertrophy [9]. In addition, studies have indicated that metabolic perturbation was involved in the process of DN, such as TCA cycle [10] and purine and pyrimidine metabolism [11]. DN is always accompanied by elevated albuminuria, renal fibrosis, and metabolic disorder.…”

Section: Introductionmentioning

confidence: 99%

Hirsutella sinensis Treatment Shows Protective Effects on Renal Injury and Metabolic Modulation in db/db Mice

Sun

et al. 2019

Evidence-Based Complementary and Alternative Medicine

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Hirsutella sinensis (HS) is the anamorph of the traditional Chinese medicine Cordyceps sinensis. Although the renal protective effect of HS has been reported, its effect on diabetic nephropathy (DN) remains unclear. In this study, db/db mice were used as the DN model, and the renal protective effect was evaluated after oral administration of HS for 6 and 12 weeks. Plasma, urine, and kidney samples were collected, and biochemical indicator measurements, pathological analysis, and metabolomics studies were performed. Biochemical assays showed that HS reduced the levels of fasting blood glucose (FBG), urinary albumin/creatinine ratio (ACR), and N-acetyl-beta-D-glucosaminidase (NAG) and increased the creatinine clearance (Ccr). HS alleviated glomerular and tubular glycogen accumulation and fibrosis and normalized the disordered ultrastructure of the glomerular filtration barrier. Metabolomics analysis of metabolites in the plasma, urine, and kidney indicated that HS modulated the perturbed glycolipid metabolism and amino acid turnover. HS reduced the elevated levels of metabolites involved in energy metabolism (TCA cycle, glycolysis, and pentose phosphate pathway) and nucleotide metabolism (pyrimidine metabolism and purine metabolism) in the kidneys of db/db mice. These results suggest that HS can protect against renal injury and that its efficacy involved metabolic modulation of the disturbed metabolome in db/db mice.

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Metabolic changes in urine and serum during progression of diabetic kidney disease in a mouse model

Cited by 12 publications

References 32 publications

Validation of Candidate Phospholipid Biomarkers of Chronic Kidney Disease in Hyperglycemic Individuals and Their Organ-Specific Exploration in Leptin Receptor-Deficient db/db Mouse

Validation of Candidate Phospholipid Biomarkers of Chronic Kidney Disease in Hyperglycemic Individuals and Their Organ-Specific Exploration in Leptin Receptor-Deficient db/db Mouse

Mitochondrial Redox Signaling and Oxidative Stress in Kidney Diseases

Hirsutella sinensis Treatment Shows Protective Effects on Renal Injury and Metabolic Modulation in db/db Mice

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