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

Am J Clin Nutr. 2009 Jan;89(1):177-84. doi: 10.3945/ajcn.2008.26559. Epub 2008 Dec 3.

Abstract

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.

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, alpha- and gamma-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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter 1
  • ATP-Binding Cassette Transporters / metabolism*
  • ATP-Binding Cassette Transporters / physiology
  • Animals
  • Biological Transport, Active
  • Caco-2 Cells
  • Cholesterol, HDL / chemistry*
  • Chromatography, High Pressure Liquid
  • Diterpenes
  • Humans
  • Intestinal Absorption
  • Mice
  • Mice, Inbred DBA
  • Mice, Transgenic
  • Nutritional Status
  • Retinyl Esters
  • Vitamin A / analogs & derivatives
  • Vitamin A / blood
  • Vitamin A / metabolism*
  • Vitamin E / blood
  • Vitamin E / metabolism*
  • alpha-Tocopherol / metabolism
  • gamma-Tocopherol / metabolism

Substances

  • ABCA1 protein, human
  • ATP Binding Cassette Transporter 1
  • ATP-Binding Cassette Transporters
  • Cholesterol, HDL
  • Diterpenes
  • Retinyl Esters
  • Vitamin A
  • Vitamin E
  • retinol palmitate
  • gamma-Tocopherol
  • alpha-Tocopherol