1. Academic Validation
  2. ABCB1 (P-glycoprotein) regulates vitamin D absorption and contributes to its transintestinal efflux

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

  • FASEB J. 2019 Feb;33(2):2084-2094. doi: 10.1096/fj.201800956R.
Marielle Margier 1 Xavier Collet 2 Cédric le May 3 Charles Desmarchelier 1 François André 4 Chantal Lebrun 5 Catherine Defoort 1 6 Alice Bluteau 5 Patrick Borel 1 Anne Lespine 5 Emmanuelle Reboul 1
Affiliations

Affiliations

  • 1 Aix Marseille Université, INSERM, Institut National de la Recherche Agronomique (INRA), Centre de Recherche on Cardiovasculaire et Nutrition (C2VN), Marseille, France.
  • 2 INSERM, Unité Mixte de Recherche (UMR) 1048, Institute of Metabolic and Cardiovascular Diseases (I2MC), Université de Toulouse III, Toulouse, France.
  • 3 Institut du Thorax, INSERM, Centre National de la Recherche Scientifique (CNRS), Université de Nantes, Nantes, France.
  • 4 Institut de Biologie Intégrative de la Cellule (I2BC), Centre National de la Recherche Scientifique (CNRS), Unité Mixte de Recherche (UMR) 9198, Commissariat à l'Energie Atomique et aux Energies Alternatives/Institut de Biologie Frédéric Joliot, Université Paris-Saclay, Gif-sur-Yvette, France.
  • 5 Innovations Thérapeutiques et Résistances (InTheRes), UMR 1436, Université de Toulouse, INRA, École Nationale Vétérinaire de Toulouse (ENVT), Toulouse, France.
  • 6 Criblage Biologique Marseille (CriBioM), Faculté de Médecine de la Timone, Marseille, France.
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 (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 was markedly decreased compared with controls. This reduction of 25(OH)D3 transfer from plasma to lumen was further confirmed in vivo in intestine-perfused mice. Docking experiments established that both D3 and 25(OH)D3 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)D3 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., le May, 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.

Keywords

25-hydroxycholecalciferol; MDR1; bioavailability; cholecalciferol; enterocyte.

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