Vitamin D intestinal absorption is not a simple passive diffusion: Evidences for involvement of cholesterol transporters

Abstract Scope : It is assumed that vitamin D is absorbed by passive diffusion. However, since cholecalciferol (vitamin D 3 ) and cholesterol display similar structures, we hypothesized that common absorption pathways may exist. Methods and results : Cholecalciferol apical transport was first examined in human Caco‐2 and transfected Human embryonic kidney (HEK) cells. Cholecalciferol uptake was then valuated ex vivo and in vivo , using either wild‐type mice, mice overexpressing Scavenger Receptor class B type I (SR‐BI) at the intestinal level or mice treated or not with ezetimibe. Cholecalciferol uptake was concentration‐, temperature‐ and direction‐dependent, and was significantly impaired by a co‐incubation with cholesterol or tocopherol in Caco‐2 cells. Moreover Block Lipid Transport‐1 (SR‐BI inhibitor) and ezetimibe glucuronide (Niemann‐Pick C1 Like 1 inhibitor) significantly decreased cholecalciferol transport. Transfection of HEK cells with SR‐BI, Cluster Determinant 36 and Niemann‐Pick C1 Like 1 significantly enhanced vitamin D uptake, which was significantly decreased by the addition of Block Lipid Transport‐1, sulfo‐ N ‐succinimidyl oleate (Cluster Determinant 36 inhibitor) or ezetimibe glucuronide, respectively. Similar results were obtained in mouse intestinal explants. In vivo , cholecalciferol uptake in proximal intestinal fragments was 60% higher in mice overexpressing SR‐BI than in wild‐type mice ( p <0.05), while ezetimibe effect remained non‐significant. Conclusion: These data show for the first time that vitamin D intestinal absorption is not passive only but involves, at least partly, some cholesterol transporters.