Vitamin D intestinal absorption is not a simple passive diffusion: Evidences for involvement of cholesterol transporters.
Mol Nutr Food Res. 2011 Jan 31. doi: 10.1002/mnfr.201000553.
Reboul E, Goncalves A, Comera C, Bott R, Nowicki M, Landrier JF, Jourdheuil-Rahmani D, Dufour C, Collet X, Borel P.
INRA, UMR1260 "Nutriments Lipidiques et Prévention des Maladies Métaboliques", Marseille, France; INSERM, U1025 "Bioavailability of Micronutrients", Marseille, France; Univ Aix-Marseille, Marseille, France. Emmanuelle.Reboul at univmed.fr.
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.
Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. PMID: 21280209