title: Respective contributions of intestinal Niemann-Pick C1-like 1 and scavenger receptor class B type I to cholesterol and tocopherol uptake: in vivo v. in vitro studies.
abstract: The intestinal absorption of cholesterol and lipid micronutrients such as vitamin E has been shown to share some common pathways. The present study aims to further compare the uptake of cholesterol ([3H]cholesterol v. 22-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-23,24-bisnor-5-cholen-3-ol (NBD-cholesterol)) and tocopherol in Caco-2 TC-7 cells and in mouse intestine, with special focus on the respective roles of scavenger receptor class B type I (SR-BI) and Niemann-Pick C1-like 1 (NPC1L1). Conversely to NBD-cholesterol, the uptakes of [3H]cholesterol and tocopherol by Caco-2 cells were impaired by both block lipid transport-1 and ezetimibe, which inhibit SR-BI and NPC1L1, respectively. These inhibitions occurred only when cholesterol or tocopherol was delivered to cells included in micelles that contained biliary acid and at least oleic acid as a lipid. In vivo, after 2 h of digestion in mice, the uptake of the two cholesterol analogues and of tocopherol all showed distinct patterns along the duodenum-jejunum axis. [3H]Cholesterol uptake, which correlated closely to NPC1L1 mRNA expression in wild-type (wt) mice, was strongly inhibited by ezetimibe. Intestinal SR-BI overexpression did not change NPC1L1 expression and led to a significant increase in [3H]cholesterol uptake in the distal jejunum. Conversely, neither ezetimibe treatment nor SR-BI overexpression had an effect on NBD-cholesterol uptake. However, in contrast with SR-BI mRNA expression, tocopherol absorption increased strongly up to the distal jejunum in wt mice where it was specifically inhibited by ezetimibe, and was increased in the proximal intestine of intestinal SR-BI-overexpressing mice. Thus, cholesterol and tocopherol uptakes share common pathways in cell culture models, but display different in vivo absorption patterns associated with distinct contributions of SR-BI and NPC1L1.
authors.affiliation: INRA, UMR1260 'Lipid Nutrients and Prevention of Metabolic Diseases', Marseille F-13385, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Reboul
authors.affiliation: INSERM, U563, Toulouse F-31024, France.
authors.forename: Zeina
authors.initials: Z
authors.lastname: Soayfane
authors.affiliation: INRA, UMR1260 'Lipid Nutrients and Prevention of Metabolic Diseases', Marseille F-13385, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Goncalves
authors.affiliation: INSERM, U563, Toulouse F-31024, France.
authors.forename: Michela
authors.initials: M
authors.lastname: Cantiello
authors.affiliation: INRA, UMR1260 'Lipid Nutrients and Prevention of Metabolic Diseases', Marseille F-13385, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Bott
authors.affiliation: INSERM, U563, Toulouse F-31024, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Nauze
authors.affiliation: INSERM, U563, Toulouse F-31024, France.
authors.forename: François
authors.initials: F
authors.lastname: Tercé
authors.affiliation: INSERM, U563, Toulouse F-31024, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Collet
authors.affiliation: INSERM, U563, Toulouse F-31024, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Coméra
mesh_terms: D009327:4-Chloro-7-nitrobenzofurazan / Q000031:analogs & derivatives* / Q000378:metabolism; D000042:Absorption; D000818:Animals; D001384:Azetidines / Q000494:pharmacology; D001647:Bile Acids and Salts / Q000378:metabolism; D018938:Caco-2 Cells; D002462:Cell Membrane / Q000378:metabolism; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003517:Cyclopentanes / Q000494:pharmacology; D004386:Duodenum / Q000378:metabolism; D000069438:Ezetimibe; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007583:Jejunum / Q000378:metabolism; D050356:Lipid Metabolism; D026901:Membrane Transport Proteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008823:Micelles; D051122:Scavenger Receptors, Class B / Q000502:physiology*; D013882:Thiosemicarbazones / Q000494:pharmacology; D013997:Time Factors; D014810:Vitamin E / Q000378:metabolism; D024504:gamma-Tocopherol / Q000378:metabolism*
chemical_list: C526651:2-hexyl-1-cyclopentanone thiosemicarbazone; C077527:7-nitrobenz-2-oxa-1,3-diazol-4-ylcholesterol; D001384:Azetidines; D001647:Bile Acids and Salts; D003517:Cyclopentanes; D026901:Membrane Transport Proteins; D008823:Micelles; C482445:Npc1l1 protein, mouse; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D013882:Thiosemicarbazones; D014810:Vitamin E; D024504:gamma-Tocopherol; D002784:Cholesterol; D000069438:Ezetimibe; D009327:4-Chloro-7-nitrobenzofurazan