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

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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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). https://doi.org/10.1007/s00394-020-02249-6

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Keywords

  • MetS-induced nephropathy
  • Vitamin D3
  • RAAS
  • DPP-4
  • GLP-1
  • SIRT1/AMPK