The Complex ABCG5/ABCG8 Regulates Vitamin D Absorption Rate and Contributes to its Efflux from the Intestine. Issue 21 (28th September 2021)

• Record Type: Journal Article
• Authors: Antoine, Tiffany; Le May, Cédric; Margier, Marielle; Halimi, Charlotte; Nowicki, Marion; Defoort, Catherine; Svilar, Ljubica; Reboul, Emmanuelle
• Is Part Of: Molecular nutrition & food research. Volume 65:Issue 21(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-09-28
• Subjects: 25‐hydroxycholecalciferol -- bile -- bioavailability -- cholecalciferol -- enterocyte -- transintestinal efflux; Food -- Biotechnology -- Periodicals; Food -- Microbiology -- Periodicals; Nutrition -- Periodicals; Food -- Toxicology -- Periodicals; Nutrition -- Periodicals; Food Microbiology -- Periodicals; Food Technology -- Periodicals; Molecular Biology -- Periodicals; 664.0705
• DOI: 10.1002/mnfr.202100617
• Languages: English
• ISSNs: 1613-4125

Abstract

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. Abstract : Cholecalciferol and 25‐hydroxycholecalciferol apical effluxes are increased in human cells overexpressing ABCG5/G8. ABCG5/G8 inactivation in mouse intestine induces an accumulation of cholecalciferol in plasma or liver, a delay in cholecalciferol postprandial response, and a decrease in 25‐hydroxycholecalciferol transfer from plasma to lumen. ABCG5/G8 thus regulates vitamin D absorption kinetics by contributing to its efflux back to the lumen and participates in vitamin D transintestinal efflux.