Combined Treatment with Omega-3 Fatty Acid and Cholecalciferol Increases 1,25-Dihydroxyvitamin D Levels by Modulating Dysregulation of Vitamin D Metabolism in 5/6 Nephrectomy Rats

Nutrients. 2019 Dec 1;11(12):2903. doi: 10.3390/nu11122903.

Abstract

The protein 1α-hydroxylase (CYP27B1) was expressed in liver and omega-3 fatty acid (FA) elevated 1,25-dihydroxyvitamin D [1,25(OH)2D] levels in dialysis patients. The aim of this study was to determine whether omega-3 FA and cholecalciferol have effects on vitamin D metabolism related to CYP27B1 and 24-hydroxylase (CYP24) activities in the kidney and liver of 5/6 nephrectomy (Nx) rats. Male Sprague-Dawley rats were divided into the following groups: sham control, 5/6 Nx, 5/6 Nx treated with cholecalciferol, 5/6 Nx treated with omega-3 FA, and 5/6 Nx treated with cholecalciferol/omega-3 FA. CYP27B1 and CYP24 expression were measured in the liver and kidney. Further, 1,25(OH)2D and 25-hydroxyvitamin D [25(OH)D] levels were measured in serum. Among Nx groups, 1,25(OH)2D and 25(OH)D levels were lowest in the 5/6 Nx group. CYP24 expression was increased in the kidney of the 5/6 Nx rat model, which was found to be reversed by omega-3 FA or cholecalciferol/omega-3 FA supplementation. Decreased CYP27B1 expression was observed in the liver of the 5/6 Nx rats and its expression was recovered by supplementation with cholecalciferol/omega-3 FA. In conclusion, omega-3 FA and cholecalciferol may synergistically increase 1,25(OH)2D levels by inhibiting CYP24 expression in the kidney and liver and activating CYP27B1 expression in the liver of 5/6 Nx rats.

Keywords: 1,25-dihydroxyvitamin D; 1α-hydroxylase (CYP27B1); 24-hydroxylase (CYP24); 25-hydroxyvitamin D; cholecalciferol; omega-3 fatty acid.

MeSH terms

  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / genetics*
  • Animals
  • Cholecalciferol / pharmacology*
  • Cytochrome P450 Family 24 / genetics*
  • Disease Models, Animal
  • Fatty Acids, Omega-3 / pharmacology*
  • Immunohistochemistry
  • Kidney / drug effects
  • Kidney / enzymology
  • Liver / drug effects
  • Liver / enzymology
  • Male
  • Nephrectomy
  • Rats
  • Rats, Sprague-Dawley
  • Vitamin D / analogs & derivatives*
  • Vitamin D / blood
  • Vitamin D / metabolism

Substances

  • Fatty Acids, Omega-3
  • Vitamin D
  • Cholecalciferol
  • 1,25-dihydroxyvitamin D
  • 25-hydroxyvitamin D
  • Cytochrome P450 Family 24
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase

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