title: Vitamin D intestinal absorption is not a simple passive diffusion: evidences for involvement of cholesterol transporters.
abstract: METHODS
  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.
  
  
  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.
  
  
  CONCLUSIONS
  These data show for the first time that vitamin D intestinal absorption is not passive only but involves, at least partly, some cholesterol transporters.
authors.affiliation: INRA, UMR1260 Nutriments Lipidiques et Prévention des Maladies Métaboliques, Marseille, France. Emmanuelle.Reboul@univmed.fr
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Reboul
authors.forename: Aurélie
authors.initials: A
authors.lastname: Goncalves
authors.forename: Christine
authors.initials: C
authors.lastname: Comera
authors.forename: Romain
authors.initials: R
authors.lastname: Bott
authors.forename: Marion
authors.initials: M
authors.lastname: Nowicki
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Landrier
authors.forename: Dominique
authors.initials: D
authors.lastname: Jourdheuil-Rahmani
authors.forename: Claire
authors.initials: C
authors.lastname: Dufour
authors.forename: Xavier
authors.initials: X
authors.lastname: Collet
authors.forename: Patrick
authors.initials: P
authors.lastname: Borel
mesh_terms: D000818:Animals; D001384:Azetidines / Q000494:pharmacology; D018955:CD36 Antigens / Q000502:physiology; D018938:Caco-2 Cells; D002762:Cholecalciferol / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism*; D003517:Cyclopentanes / Q000494:pharmacology; D004058:Diffusion; D020719:Glucuronides / Q000494:pharmacology; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects; D008297:Male; D008565:Membrane Proteins / Q000502:physiology; D026901:Membrane Transport Proteins / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018102:Receptors, Leukotriene B4 / Q000378:metabolism; D051122:Scavenger Receptors, Class B / Q000502:physiology; D013882:Thiosemicarbazones / Q000494:pharmacology
chemical_list: C526651:2-hexyl-1-cyclopentanone thiosemicarbazone; D001384:Azetidines; D018955:CD36 Antigens; D003517:Cyclopentanes; D020719:Glucuronides; C513240:LTB4R protein, human; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C410800:NPC1L1 protein, human; D018102:Receptors, Leukotriene B4; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; D013882:Thiosemicarbazones; C511436:ezetimibe glucuronide; D002762:Cholecalciferol; D002784:Cholesterol