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.

Su Mi Lee,Young Ki Son,Seong Eun Kim,Mi Hwa Lee,Won Suk An

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.

Highlights

Vitamin D deficiency is very frequent among chronic kidney disease (CKD) patients and has been associated with increased mortality as well as faster progression of CKD [1,2]
Compared with levels in the 5/6 Nx group, the 25(OH)D levels were increased in 5/6 Nx rats treated with omega-3 fatty acid (FA)
5/6 Nx groups, the serum 25(OH)D and 1,25(OH)2 D levels were the highest in 5/6 Nx rats treated with cholecalciferol and omega-3 FA

Summary

Introduction

Vitamin D deficiency is very frequent among chronic kidney disease (CKD) patients and has been associated with increased mortality as well as faster progression of CKD [1,2]. 1α-hydroxylase (CYP27B1) activity with reduced kidney function in CKD contributes to a gradual decrease in 1,25-dihydroxyvitamin D [1,25(OH) D] levels [3]. 24-hydroxylase (CYP24) is associated with vitamin D catabolism in CKD [3]. CYP27B1 and CYP24 in proximal tubules of kidney play an important role in vitamin D metabolism in CKD [4]. One study reported that CYP27B1 was strongly presented in monocytes that develop into Kupffer cells [5]. Recent studies reported that CYP24 is expressed in hepatocytes [6,7]. Rat models of ageing and long-term diabetes mellitus showed significantly increased expression of CYP24 in hepatocytes, as well as in non-hepatocytes including Kupffer cells, hepatic stellate cells, and sinusoidal endothelial cells [7]. Extrarenal 1,25(OH) D production has previously been reported in anephric

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