Vitamin D Status of Mice Deficient in Scavenger Receptor Class B Type 1, Cluster Determinant 36 and ATP-Binding Cassette Proteins G5/G8.

Mikis Kiourtzidis,Gabriele I Stangl,Corinna Brandsch,Julia Kühn

doi:10.3390/nu12082169

Abstract

Classical lipid transporters are suggested to modulate cellular vitamin D uptake. This study investigated the vitamin D levels in serum and tissues of mice deficient in SR-B1 (Srb1-/-), CD36 (Cd36-/-) and ABC-G5/G8 (Abcg5/g8-/-) and compared them with corresponding wild-type (WT) mice. All mice received triple-deuterated vitamin D3 (vitamin D3-d3) for six weeks. All knockout mice vs. WT mice showed specific alterations in their vitamin D concentrations. Srb1-/- mice had higher levels of vitamin D3-d3 in the serum, adipose tissue, kidney and heart, whereas liver levels of vitamin D3-d3 remained unaffected. Additionally, Srb1-/- mice had lower levels of deuterated 25-hydroxyvitamin D3 (25(OH)D3-d3) in the serum, liver and kidney compared to WT mice. In contrast, Cd36-/- and WT mice did not differ in the serum and tissue levels of vitamin D3-d3, but Cd36-/- vs. WT mice were characterized by lower levels of 25(OH)D3-d3 in the serum, liver and kidney. Finally, Abcg5/g8-/- mice tended to have higher levels of vitamin D3-d3 in the serum and liver. Major alterations in Abcg5/g8-/- mice were notably higher levels of 25(OH)D3-d3 in the serum and kidney, accompanied by a higher hepatic mRNA abundance of Cyp27a1 hydroxylase. To conclude, the current data emphasize the significant role of lipid transporters in the uptake, tissue distribution and activation of vitamin D.

Highlights

Most vitamin D in the body is synthesized from cutaneous 7-dehydrocholesterol (7-DHC) via ultraviolet B (UVB) light exposure
No differences in the absolute and relative liver weights were observed between the Srb1-/- or Cd36-/- mice and their corresponding WT counterparts, whereas higher absolute and relative liver weights were observed in Abcg5/g8-/- mice than in the corresponding
Serum levels of aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) did not differ between knockout mice and the corresponding WT mice (Table 1), assuming that the higher liver weights of Abcg5/g8-/- mice are not indicative of liver injury

Summary

Introduction

Most vitamin D in the body is synthesized from cutaneous 7-dehydrocholesterol (7-DHC) via ultraviolet B (UVB) light exposure. Due to seasonal fluctuations in the intensity of UVB radiation or situations that limit the endogenous synthesis of vitamin D, many individuals are at high risk of developing vitamin D deficiency. Several health authorities have established guidelines on vitamin D intake to prevent or treat vitamin D deficiency [1,2,3,4,5]. The regular intake of a vitamin D supplement is a common and efficient strategy to improve vitamin D status. Despite the widespread use of vitamin D supplements, there is insufficient knowledge on the intestinal absorption and cellular uptake of orally ingested vitamin D. In vitro and ex vivo data from Reboul and coworkers indicate a role of cholesterol transporters in vitamin D uptake [6]

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