ABCB1 (P‐glycoprotein) regulates vitamin D absorption and contributes to its transintestinal efflux

Abstract

ABSTRACT Efficient intestinal absorption of dietary vitamin D is 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 (D 3 ) and 25‐hydroxycholecalciferol [25(OH)D 3 ] 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)D 3 in plasma, intestine, brain, liver, and kidneys, together with an increased D 3 postprandial response after gavage compared with controls. 25(OH)D 3 efflux through Abcb1 −/− intestinal expiants was markedly decreased compared with controls. This reduction of 25(OH)D 3 transfer from plasma to lumen was further confirmed in vivo in intestine‐perfused mice. Docking experiments established that both D 3 and 25(OH)D 3 could bind with high affinity to Caenorhabditis elegans P‐glycoprotein, used as an ABCB1 model. Finally, in a group of 39 healthy male adults, a single‐nucleotide polymorphism (SNP) in ABCB1 (rs17064) was significantly associated with the fasting plasma 25(OH)D 3 concentration. Thus, we showed here for the first time that ABCB1 is involved in neo‐absorbed vitamin D efflux by the enterocytes and that it also contributes to vitamin D transintestinal excretion and likely impacts vitamin D status.—Margier, M., Collet, X., leMay, C., Desmarchelier, C., André, F., Lebrun, C., Defoort, C., Bluteau, A., Borel, P., Lespine, A., Reboul, E. ABCB1 (P‐glycoprotein) regulates vitamin D absorption and contributes to its transintestinal efflux. FASEB J. 33, 2084–2094 (2019). www.fasebj.org