ABCG1 is involved in vitamin E efflux

• We investigated the possible participation of ABCG1 in cellular vitamin E efflux.
• Abcg1-deficient mice displayed abnormal lipoprotein and tissue vitamin E content.
• ABCG1 was involved in vitamin E efflux from CHO, Hep3B and THP-1 cells.
• Vitamin E significantly downregulated ABCG1 mRNA levels in cell models and in rats.
• Vitamin E significantly decreased oxysterol content in Hep3B and in rat liver.

Vitamin E membrane transport has been shown to involve the cholesterol transporters SR-BI, ABCA1 and NPC1L1. Our aim was to investigate the possible participation of another cholesterol transporter in cellular vitamin E efflux: ABCG1. In Abcg1-deficient mice, vitamin E concentration was reduced in plasma lipoproteins whereas most tissues displayed a higher vitamin E content compared to wild-type mice. α- and γ-tocopherol efflux was increased in CHO cells overexpressing human ABCG1 compared to control cells. Conversely, α- and γ-tocopherol efflux was decreased in ABCG1-knockdown human cells (Hep3B hepatocytes and THP-1 macrophages). Interestingly, α- and γ-tocopherol significantly downregulated ABCG1 and ABCA1 expression levels in Hep3B and THP-1, an effect confirmed in vivo in rats given vitamin E for 5 days. This was likely due to reduced LXR activation by oxysterols, as Hep3B cells and rat liver treated with vitamin E displayed a significantly reduced content in oxysterols compared to their respective controls. Overall, the present study reveals for the first time that ABCG1 is involved in cellular vitamin E efflux.