ATP-binding cassette transporter A1 is significantly involved in the intestinal absorption of alpha- and gamma-tocopherol but not in that of retinyl palmitate in mice.
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 alpha-tocopherol is secreted with intestinal HDL.


OBJECTIVE
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, alpha- and gamma-tocopherol) and in that of retinyl palmitate (vitamin A).


METHODS
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 alpha- and gamma-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 alpha- and gamma-tocopherol was also impaired by glyburide and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid. The postprandial response of plasma gamma-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 alpha-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 alpha- and gamma-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.
Reboul
Emmanuelle
E
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.
Trompier
Doriane
D
Moussa
Myriam
M
Klein
Alexis
A
Landrier
Jean-François
JF
Chimini
Giovanna
G
Borel
Patrick
P
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D001693:Biological Transport, Active; D018938:Caco-2 Cells; D008076:Cholesterol, HDL / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D004224:Diterpenes; D006801:Humans; D007408:Intestinal Absorption; D051379:Mice; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D009752:Nutritional Status; D000084562:Retinyl Esters; D014801:Vitamin A / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism*; D014810:Vitamin E / Q000097:blood / Q000378:metabolism*; D024502:alpha-Tocopherol / Q000378:metabolism; D024504:gamma-Tocopherol / Q000378:metabolism
C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D008076:Cholesterol, HDL; D004224:Diterpenes; D000084562:Retinyl Esters; D014801:Vitamin A; D014810:Vitamin E; C014794:retinol palmitate; D024504:gamma-Tocopherol; D024502:alpha-Tocopherol