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

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) and 25-hydroxycholecalciferol [25(OH)D] 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 in plasma, intestine, brain, liver, and kidneys, together with an increased D postprandial response after gavage compared with controls. 25(OH)D efflux through Abcb1 intestinal explants was markedly decreased compared with controls. This reduction of 25(OH)D transfer from plasma to lumen was further confirmed in vivo in intestine-perfused mice. Docking experiments established that both D and 25(OH)D 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 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.

Vitamin D Binding Protein: A Historic Overview

“…Vitamin D from dietary origin is absorbed in the intestine with about 70% efficacy in normal subjects. Although this process was for a long time considered to be a passive transport of a lipophilic molecule to access the lipid layer of the intestinal cells (82), more recent data suggest that vitamin D absorption and secretion from and into the lumen of the gut is medicated by carrier proteins that are also involved in cholesterol transport in the intestine (83). To what extent vitamin D esters are first digested and then absorbed or lost in the feces is still a point of discussion [see Solanum malacoxylon being a 1,25(OH) 2 D-glucuronide causing severe generalized calcinosis in grazing cattle in Argentina (84,85)].…”

Mechanisms of Carotenoid Intestinal Absorption: Where Do We Stand?

“…Besides SR-BI, ABCB1 (ATP binding cassette B1, also known as P-glycoprotein) and ABCG transporters, such as ABCG5, appear as good candidates. Indeed, a recent study combining in silico, cell culture, animal, and genetic approaches showed that ABCB1 was involved in vitamin D intestinal efflux [51]. Additionally, polymorphisms in the ABCG5 gene tended to contribute to individual response to lutein supplementation in humans [52].…”

Genetic factors involved in the bioavailability of tomato carotenoids

“…ABCB1 encodes for the P-glycoprotein, an ATP-dependent drug efflux pump for xenobiotics with broad substrate specificity, highly expressed in enterocytes. The association of P-glycoprotein with postprandial lycopene concentrations suggests that it could participate in the efflux of lycopene back to the intestinal lumen, as was recently shown for vitamin D [61]. ELOVL2 encodes for ELOVL fatty acid elongase 2 which catalyzes the elongation of eicosapentaenoic acid to docosapentaenoic acid and docosapentaenoic acid to docosahexaenoic acid.…”