Renoprotective effects of vitamin D3 supplementation in a rat model of metabolic syndrome



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.


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.


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.


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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Advanced glycation end products


5′Adenosine monophosphate-activated protein kinase

Ang II:

Angiotensin II


Analysis of variance


Ang II type 1 receptor


Area under the curve


Body mass index


Body weight


Chronic kidney disease


1,25-Dihydroxy vitamin D3


Dipeptidyl peptidase-4


Enzyme-linked immunosorbent assay


Fasting serum glucose


Fasting serum insulin


Glucagon-like peptide-1


Hematoxylin and eosin


Hemoglobin A1c


High-density lipoprotein cholesterol


Homeostasis Model Assessment of Insulin Resistance


Insulin resistance


Low-density lipoprotein cholesterol


Mitogen-activated protein kinase




Metabolic syndrome

NAD+ :

Nicotinamide adenine dinucleotide


Nicotinamide adenine dinucleotide phosphate


Oral glucose tolerance test




Renin angiotensin aldosterone system


Reactive oxygen species


Standard error of the mean




Total cholesterol




Transforming growth factor-β1


Tumor necrosis factor-α


Urinary albumin/creatinine ratio


Vitamin D receptor


Waist circumference


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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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Correspondence to Nehal S. Wahba.

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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).

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  • MetS-induced nephropathy
  • Vitamin D3
  • RAAS
  • DPP-4
  • GLP-1