The Complex ABCG5/ABCG8 Regulates Vitamin D Absorption Rate and Contributes to its Efflux from the Intestine

Abstract

Scope: Most people are vitamin D insufficient around the world. Vitamin D intestinal absorption should thus be optimized. The role of the ATP-binging cassette G5/G8 (ABCG5/G8) heterodimer in vitamin D intestinal efflux is investigated. Methods and Results: Both cholecalciferol and 25-hydroxycholecalciferol apical effluxes are increased by ABCG5/G8 overexpression in human Griptite cells. Mice deficient in ABCG5/G8 at the intestinal level (I-Abcg5/g8 −/− mice) display an accumulation of cholecalciferol in plasma in females and in liver in males compared to control animals. I-Abcg5/g8 −/− mice display a delay in cholecalciferol postprandial response after gavage compared with controls. 25-Hydroxycholecalciferol transfer from plasma to lumen is observed in vivo in intestine-perfused mice, and the lack of intestinal ABCG5/G8 complex induces a decrease in this efflux, while vitamin D bile excretion remains unchanged. Conclusion: Overall, it is showed for the first time that the ABCG5/G8 heterodimer regulates the kinetics of absorption of dietary vitamin D by contributing to its efflux back to the lumen, and that it also participates in vitamin D transintestinal efflux.

ABCG5 and ABCG8 Are Involved in Vitamin K Transport

“…In addition to sterols, NPC1L1 absorbs vitamin K in the intestine [ 12 ]. Since substrate specificities of NPC1L1 and ABCG5/ABCG8 are similar, we speculated that ABCG5/ABCG8 also transports vitamin K. Recently, ABCG5/ABCG8 has been reported to transport vitamin D in the intestine [ 13 ]. This supports the idea that ABCG5/ABCG8 transports fat-soluble vitamins, such as vitamin K.…”