ABCB1 is involved in vitamin D intestinal efflux

Cholecalciferol, 25-hydroxycholecalciferol, intestine, excretionCholecalciferol, 25-hydroxycholecalciferol, intestine, excretionRecently, a new pathway for cholesterol elimination has been discovered: the transintestinal cholesterol excretion (TICE). This phenomenon involves ABCB1 (ATP-binding cassette B1). Vitamin D3 (cholecalciferol) has been shown to be absorbed by enterocytes via cholesterol transporters. It may thus be excreted by pathways similar to those of cholesterol. As vitamin D is essential for calcium and phosphate homeostasis, immune system and vascular risk prevention, this situation should be considered for patients whose TICE would be activated. The aim of this study was thus to assess the contribution of ABCB1 to the intestinal efflux of vitamin D (cholecalciferol and its metabolite 25-hydroxyvitamin D (25(OH)D). Cholecalciferol and 25(OH) D efflux by cells transfected either stably or transiently with the ABCB1 gene was measured. 25(OH)D status in abcb1-deficient mice was compared to that of wild mice. Their postprandial plasma cholecalciferol response was then assessed following cholecalciferol gavage. Besides, the intestine ability to excrete cholecalciferol and 25(OH)D was estimated using Ussing chambers and via in situ perfusion experiments. Finally, 39 healthy adult men were genotyped using whole-genome microarrays. The association between SNPs in genes involved in vitamin D and lipid metabolism and the 25(OH) status was analyzed by partial least squares regression (PLS regression). The data collected showed that cells overexpressing ABCB1 had a better capacity to excrete cholecalciferol and 25(OH)D compared to control cells (+167% for cholecalciferol and +150% for 25(OH)D; p<0.05). These results were confirmed by Ussing chambers (p<0.05). In vivo, Abcb1-deficient mice displayed fasting plasma 25(OH)D concentrations 30% higher than wild type mice (p<0.05). The postprandial cholecalciferol response in abcb1-deficient mice was also twice higher than in wild mice (p