Abstract
Purpose
The study aimed to investigate the potential nephroprotective effects of vitamin D3 in metabolic syndrome (MetS) and the molecular basis of the underlying mechanisms of its action.
Methods
MetS was induced in adult male Wistar rats by adding fructose (10%) to every day drinking water and salt (3%) to the diet. Six weeks after fructose/salt consumption, fasting serum lipid profile and uric acid levels were determined, an oral glucose tolerance test (OGTT) was performed and kidney function was checked. MetS rats were then treated orally with vitamin D3 (10 µg/kg/day) for 6 weeks. At the end of the study period (12 weeks), the OGTT test was reperformed, anthropometrical parameters were measured, urine, blood and tissue samples were collected and the animals were euthanised.
Results
The incidence of MetS was confirmed 6 weeks after fructose/salt consumption, when the rats exhibited significant weight gain, dyslipidemia, hyperuricemia, insulin resistance, hyperinsulinemia and impaired glucose tolerance. After 12 weeks, MetS rats displayed markedly declined renal function alongside with extravagant renal histopathological damages and interstitial fibrosis. Furthermore, significantly enhanced renal oxidative stress and inflammation were manifested. Vitamin D3 supplementation in MetS rats significantly reversed all the above-mentioned deleterious effects.
Conclusion
The study has indeed provided mounting evidence of the promising therapeutic potential of vitamin D3 against development and progression of MetS-induced nephropathy. A new insight has been introduced into the crucial role of dipeptidyl peptidase-4 inhibition and sirtuin-1/5′adenosine monophosphate-activated protein kinase activation in the renoprotective effects of vitamin D3.
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Abbreviations
- AGEs:
-
Advanced glycation end products
- AMPK:
-
5′Adenosine monophosphate-activated protein kinase
- Ang II:
-
Angiotensin II
- ANOVA:
-
Analysis of variance
- ATIR:
-
Ang II type 1 receptor
- AUC:
-
Area under the curve
- BMI:
-
Body mass index
- BW:
-
Body weight
- CKD:
-
Chronic kidney disease
- 1,25(OH)2D3:
-
1,25-Dihydroxy vitamin D3
- DPP-4:
-
Dipeptidyl peptidase-4
- ELISA:
-
Enzyme-linked immunosorbent assay
- FSG:
-
Fasting serum glucose
- FSI:
-
Fasting serum insulin
- GLP-1:
-
Glucagon-like peptide-1
- H&E:
-
Hematoxylin and eosin
- HbA1c:
-
Hemoglobin A1c
- HDL-C:
-
High-density lipoprotein cholesterol
- HOMA-IR:
-
Homeostasis Model Assessment of Insulin Resistance
- IR:
-
Insulin resistance
- LDL-C:
-
Low-density lipoprotein cholesterol
- MAPK:
-
Mitogen-activated protein kinase
- MDA:
-
Malondialdehyde
- MetS:
-
Metabolic syndrome
- NAD+ :
-
Nicotinamide adenine dinucleotide
- NADPH:
-
Nicotinamide adenine dinucleotide phosphate
- OGTT:
-
Oral glucose tolerance test
- P/T:
-
Phosphorylated/total
- RAAS:
-
Renin angiotensin aldosterone system
- ROS:
-
Reactive oxygen species
- S.E.M:
-
Standard error of the mean
- SIRT1:
-
Sirtuin-1
- TC:
-
Total cholesterol
- TG:
-
Triglycerides
- TGF-β1:
-
Transforming growth factor-β1
- TNF-α:
-
Tumor necrosis factor-α
- UACR:
-
Urinary albumin/creatinine ratio
- VDR:
-
Vitamin D receptor
- WC:
-
Waist circumference
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Acknowledgements
No financial support was received. The authors acknowledge Prof. Dr. Dina Sabry, Professor of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Cairo University, for her valuable help in performing the molecular biology analysis.
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We confirm that this study has been approved by the Ethical Committee for Animal Handling at Zagazig University and has therefore been performed in accordance with the National Institutes of Health guide for the care and use of laboratory animals.
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Wahba, N.S., Ghareib, S.A., Abdel-Ghany, R.H. et al. Renoprotective effects of vitamin D3 supplementation in a rat model of metabolic syndrome. Eur J Nutr 60, 299–316 (2021). https://doi.org/10.1007/s00394-020-02249-6
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DOI: https://doi.org/10.1007/s00394-020-02249-6