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

Mol Nutr Food Res. 2021 Nov;65(21):e2100617. doi: 10.1002/mnfr.202100617. Epub 2021 Sep 28.

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.

Keywords: 25-hydroxycholecalciferol; bile; bioavailability; cholecalciferol; enterocyte; transintestinal efflux.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 5 / genetics
  • ATP Binding Cassette Transporter, Subfamily G, Member 8 / genetics
  • ATP-Binding Cassette Transporters / genetics
  • Animals
  • Female
  • Humans
  • Intestines
  • Lipoproteins* / metabolism
  • Liver / metabolism
  • Male
  • Mice
  • Vitamin D*

Substances

  • ABCG5 protein, human
  • ABCG5 protein, mouse
  • ABCG8 protein, human
  • ABCG8 protein, mouse
  • ATP Binding Cassette Transporter, Subfamily G, Member 5
  • ATP Binding Cassette Transporter, Subfamily G, Member 8
  • ATP-Binding Cassette Transporters
  • Lipoproteins
  • Vitamin D