ABCB1 (P-glycoprotein) regulates Vitamin D absorption and contributes to its transintestinal efflux

Abstract

Efficient intestinal absorption ofdietary vitaminDis required in most people to ensure an adequate status. Thus, we investigated the involvement of ATP binding cassette subfamily B member 1 (ABCB1) in Vitamin D intestinal efflux. Both cholecalciferol (D3) and 25-hydroxycholecalciferol [25(OH)D3] apical effluxes were decreased by chemical inhibition of ABCB1 in Caco-2 cells and increased by ABCB1 overexpression in Griptites or Madin- Darby canine kidney type II cells.Mice deficient for the 2 murine ABCB1s encoded by Abcb1a and Abcb1b genes (Abcb1-/-) displayed an accumulation of 25(OH)D3 in plasma, intestine, brain, liver, and kidneys, together with an increased D3 postprandial response after gavage compared with controls. 25(OH)D3 efflux through Abcb1-/- intestinal explants wasmarkedly decreased compared with controls. This reduction of 25(OH)D3 transfer from plasma to lumenwas further confirmedin vivoin intestine-perfused mice.Docking experiments established that bothD3and 25(OH)D3 could bindwith high affinity to Caenorhabditis elegans P-glycoprotein, used as anABCB1 model. Finally, in a group of 39 healthymale adults, a single-nucleotide polymorphism (SNP) in ABCB1 (rs17064) was significantly associated with the fasting plasma 25(OH)D3 concentration. Thus, we showed here for the first time that ABCB1 is involved in neo-absorbed vitaminDefflux by the enterocytesand that it also contributes tovitaminDtransintestinal excretion and likely impacts Vitamin D status.