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ATP-binding cassette transporter A1 is significantly involved in the intestinal absorption of - and -tocopherol but not in that of retinyl palmitate in mice^1,2,3

¹ From INRA, UMR1260 "Nutriments Lipidiques et Prévention des Maladies Métaboliques", INSERM, U476, Université Aix-Marseille 1, Université Aix-Marseille 2, Faculté de Médecine, IPHM-IFR 125, Marseille, France (ER, MM, J-FL, and PB); the Centre d'Immunologie de Marseille Luminy, INSERM/CNRS, Université Aix-Marseille, Parc Scientifique de Luminy, Marseille, France (DT and GC); and INSERM, U866, IFR Santé-STIC, Faculté de Médecine, Université de Bourgogne, Dijon, France (AK).

² The work at the Centre d'Immunologie de Marseille Luminy was supported by institutional grants from INSERM and CNRS and specific grants (FLIPPASE/MPCM) from the European Community. DT was supported in part by a fellowship allocated by the Nouvelle Société Française d'Athérosclérose/Pfizer.

³ Reprints not available. Address correspondence to P Borel, UMR 476/1260 INRA, Faculté de Medécine, 27 Boulevard Jean-Moulin, 13385 Marseille, Cedex 5, France. E-mail: patrick.borel{at}univmed.fr.

Background: It has long been assumed that newly absorbed vitamin A and E enter the body only via enterocyte-produced chylomicrons. However, recent results in cell cultures have shown that a fraction of -tocopherol is secreted with intestinal HDL.

Objectives: The aims of this study were to identify this transporter and to assess whether it is significantly implicated in the in vivo intestinal absorption of the 2 main dietary forms of vitamin E (ie, - and -tocopherol) and in that of retinyl palmitate (vitamin A).

Design: Having performed preliminary experiments in the Caco-2 cell model, we compared fasting and postprandial plasma concentrations of vitamins A and E in mice deficient in ATP-binding cassette A1 (ABCA1) transporter and in wild-type mice.

Results: A substantial efflux of - and -tocopherol, but not of retinyl esters, was induced by the presence of apolipoprotein A-I at the basolateral side of Caco-2 monolayers. The efflux of - and -tocopherol was also impaired by glyburide and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid. The postprandial response of plasma -tocopherol was 4-fold lower in ABCA1^–/– mice (P = 0.025) than in wild-type mice, whereas no significant difference was observed for retinyl esters. Fasting plasma -tocopherol, but not vitamin A, concentrations were lower in mice bearing the genetic deletion.

Conclusions: ABCA1 is the transporter responsible for the in vivo secretion of - and -tocopherol with intestinal HDL, and this pathway is significantly implicated in the intestinal absorption and plasma status of vitamin E but not of vitamin A.