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International audience; Scope Most people are vitamin D insufficient around the world. Vitamin D intestinal absorption should thus be optimized. The role of the ATP-binging cassette G5/G8 (ABCG5/G8) heterodimer in vitamin D intestinal efflux is investigated. Methods and Results Both cholecalciferol and 25-hydroxycholecalciferol apical effluxes are increased by ABCG5/G8 overexpression in human Griptite cells. Mice deficient in ABCG5/G8 at the intestinal level (I-Abcg5/g8(-/-) mice) display an accumulation of cholecalciferol in plasma in females and in liver in males compared to control animals. I-Abcg5/g8(-)(/)(-) mice display a delay in cholecalciferol postprandial response after gavage compared with controls. 25-Hydroxycholecalciferol transfer from plasma to lumen is observed in vivo in intestine-perfused mice, and the lack of intestinal ABCG5/G8 complex induces a decrease in this efflux, while vitamin D bile excretion remains unchanged. Conclusion Overall, it is showed for the first time that the ABCG5/G8 heterodimer regulates the kinetics of absorption of dietary vitamin D by contributing to its efflux back to the lumen, and that it also participates in vitamin D transintestinal efflux.

International audience; Scope The effect of vitamin A deficiency on vitamin A and lipid postprandial metabolism in young rats is addressed, considering the effect of sex. Methods and Results Sprague-Dawley rats are fed either 400 UI.kg(-1) vitamin A diet (vitamin A-deficient (VAD) diet) or 2300 UI.kg(-1) vitamin A (control diet), before being mated. Mothers receive the same VAD or control diet during gestation and lactation. Offspring receive the same diet than mothers until 8 weeks of age. VAD diet-fed female and male offspring display a severe vitamin A deficiency with no body weight or glucose tolerance defects. Fasting plasma triglyceride concentrations are decreased in VAD diet-fed animals compared to controls (p < 0.05). Retinyl ester postprandial responses after vitamin A gavage, expressed as area under the curves, are not different in VAD diet-fed and control animals, although retinyl ester postprandial peak is significantly delayed (p < 0.05) in VAD diet-fed rats. Lipids also accumulate in the distal part of the intestine after gavage and [1-C-13]-oleate postprandial response is decreased in VAD diet-fed males. Conclusion Vitamin A deficiency modulates both vitamin A absorption rate and lipid postprandial metabolism, which can partly explain the altered fasting lipid status observed in VAD diet-fed offspring.

International audience; Scope: To investigate the formation and absorption of lycopene (LYC) metabolites in the human upper gastrointestinal lumen, in the absence and presence of iron. Methods: Healthy males (n = 7) consumed test meals that deliver ≈22 mg LYC + ≈0.3 mg apo-lycopenals from oleoresin without (-FeSO4) and with ferrous sulfate (160 mg, +FeSO4). Subjects were intubated with a naso-gastric/naso-duodenal tube. Digesta, blood plasma, and the triglyceride-rich lipoprotein (TRL) fractions of plasma were analyzed using LC–MS/MS, to measure LYC and apo-lycopenoids. Results: Digesta LYC concentrations increased with time (p = 1.2 × 10−7), decrease with time × iron (p = 1.1 × 10−5), and remain ≈200× higher than apo-lycopenals/lycopenone. Digesta apo-8′-, -10′-, -12′-, -14′-, -15-lycopenal, and apo-13-lycopenone concentrations increased with time (p < 0.01), apo-12′-, -14′-, -15-lycopenal, apo-13-lycopenone increase with iron (p < 0.05), and time × iron decrease apo-8′-, -10′-, -12′-, -14′-, -15-lycopenal, apo-13-lycopenone concentrations (p < 0.01). A 1.9-fold decrease in LYC TRL area-under-the-time-concentration-curve is observed after the test meal +FeSO4 versus the test meal –FeSO4 (p = 0.02). Apo-lycopenals were detected in later TRL fractions, and no apo-lycopenols or apo-lycopenoic acids were observed in any samples. Conclusions: FeSO4 reduces LYC absorption. Apo-lycopenals appear to be absorbed from foods, and not made in significant quantities during digestion.

International audience; Scope : It is widely advised to increase pulse consumption. However, pulses are rich in molecules displaying lipid‐lowering properties, including fibers, phytates, saponins and tannins. We thus explored the effects of pulses on fat‐soluble vitamin bioavailability. Methods : We assessed vitamin A (β‐carotene and retinyl‐palmitate), vitamin E (α‐tocopherol), vitamin D (cholecalciferol) and vitamin K (phylloquinone) bioaccessibility, i.e. micellarization after in vitro digestion of meals containing either potatoes (control), household‐cooked or canned pulses. The obtained mixed micelles were delivered to Caco‐2 cells to evaluate vitamin uptake. We then specifically assessed the impact of fibers, phytates, saponins and tannins on both phylloquinone (used as a model vitamin) bioaccessibility and uptake. Results : The presence of pulses significantly decreased both vitamin bioaccessibility (up to ‐65% for β‐carotene, ‐69% for retinyl‐palmitate, ‐45% for cholecalciferol, ‐53% for α‐tocopherol and ‐67% for phylloquinone) and uptake (‐40% for retinyl‐palmitate, ‐67% for cholecalciferol, ‐50% for α‐tocopherol and ‐57% for phylloquinone). Effects on bioaccessibility, but not on uptake, were dependent on pulse cooking method. Phylloquinone bioaccessibility was specifically impacted by saponins, tannins and fibers while its uptake was impacted by saponins, fibers and phytates. Conclusion : Pulses can alter fat‐soluble micronutrient bioavailability. Pulses should thus be cooked appropriately and consumed within micronutrient‐rich meals.

International audience; Vitamin E membrane transport has been shown to involve the cholesterol transporters SR-BI, ABCA1 and NPC1L1. Our aim was to investigate the possible participation of another cholesterol transporter in cellular vitamin E efflux: ABCG1. In Abcg1-deficient mice, vitamin E concentration was reduced in plasma lipoproteins whereas most tissues displayed a higher vitamin E content compared to wild-type mice. alpha- and gamma-tocopherol efflux was increased in CHO cells overexpressing human ABCG1 compared to control cells. Conversely, alpha- and gamma-tocopherol efflux was decreased in ABCG1-knockdown human cells (Hep3B hepatocytes and THP-1 macrophages). Interestingly, alpha- and gamma-tocopherol significantly downregulated ABCG1 and ABCA1 expression levels in Hep3B and THP-1, an effect confirmed in vivo in rats given vitamin E for 5 days. This was likely due to reduced LXR activation by oxysterols, as Hep3B cells and rat liver treated with vitamin E displayed a significantly reduced content in oxysterols compared to their respective controls. Overall, the present study reveals for the first time that ABCG1 is involved in cellular vitamin E efflux. (C) 2014 Elsevier B.V. All rights reserved.

International audience; Scope: A single nucleotide polymorphism in the cluster determinant 36 (CD36) gene has recently been associated with plasma alpha-tocopherol concentration, suggesting a possible role of this protein in vitamin E intestinal absorption or tissue uptake. Methods and results: To investigate the involvement of CD36 in vitamin E transport, we first evaluated the effect of CD36 on alpha- and gamma-tocopherol transmembrane uptake and efflux using transfected HEK cells. gamma-Tocopherol postprandial response was then assessed in CD36-deficient mice compared with wild-type mice, after the mice had been fully characterized for their alpha -tocopherol, vitamin A and lipid plasma, and tissue contents. Both alpha- and gamma-tocopherol uptake was significantly increased in cells overexpressing CD36 compared with control cells. Compared with wild-typemice, CD36-deficient mice displayed a significantly decreased cholesterol hepatic concentration, and males exhibited significantly higher triacylglycerol contents in liver, brain, heart, and muscle. Although tissue alpha -tocopherol concentration after adjustment for lipid content was not modified, gamma-tocopherol postprandial response was significantly increased in CD36-deficient mice compared with controls, likely reflecting the postprandial hypertriglyceridemia observed in these mice. Conclusion: Our findings show for the first time that CD36 participates-directly or indirectly-in vitamin E uptake, and that CD36 effect on postprandial lipid metabolism in turn modifies vitamin E postprandial response.

International audience; Background: Most people require dietaryvitamin D to achieve the recommended concentration of 25-hydroxyvitamin D [25(OH)D] in the blood. However, the response to vitamin D supplementation is highly variable among individuals. Objective: We assessed whether the variability in cholecalciferol bioavailability was associated with single-nucleotide polymorphisms (SNPs) in candidate genes. Methods: In a single-group design, 39 healthy adult men with a mean +/- SD age of 33 +/- 2 y and mean +/- SD body mass index lid kg/m(2)) of 22.9 +/- 0.3 were genotyped with the use of whole-genome microarrays. After an overnight fast, plasma 25(OH)D status was measured, and the subjects then consumed a meal that provided 5 mg cholecalciferol as a supplement. Plasma chylomicron cholecalciferol concentration was measured over 8 h, and cholecalciferol response was assessed by calculating the postprandial area under the curve. Partial least squares regression was used to test the association of SNPs in or near candidate genes (61 genes representing 3791 SNPs) with the postprandial cholecalciferol response. Results: The postprandial chylomicron cholecalciferol concentration peaked at 5.4 h. The cholecalciferol response was extremely variable among individuals (CV: 47%). It correlated with the chylomicron triglyceride (TG) response (r = 0.60; P < 0.001) but not with the fasting plasma 25(OH)D concentration (r = 0.04; P = 0.83). A significant (P = 1.32 x 10(-4)) partial least squares regression model that included 17 SNPs in 13 genes (including 5 that have been associated with chylomicron TG response) was associated with the variance in the cholecalciferol response. Conclusion: In healthy men, there is a high interindividual variability in cholecalciferol bioavailability that is associated with a combination of SNPs located in or near genes involved in both vitamin D and lipid metabolism. This trial was registered at clinicaltrials.gov as NCT02100774.

International audience; ScopeThe ability of different plant sterols/stanols (PS) mixtures, which differed in the degree of B-ring saturation and aliphatic side chain structure and saturation, to reduce cholesterol (CH) micellarization was explored. Methods and resultsExperiments were performed using an in vitro digestion model, synthetic mixed micelles, and pure porcine pancreatic lipases. Sterols were measured by GC-FID. The ability of PS to reduce CH micellarization was dependent on the form of PS and on the type of delivery matrix (low-fat yogurt or olive oil). Long-chain PS esters delivered in the yogurt matrix, and medium chain PS esters delivered in olive oil provided the greatest reduction in CH micellarization. In yogurt, the ability to impair CH micellarization was inversely related (rho = -0.41, p < 0.0005) to PS melting point. In olive oil, the more hydrophobic PS mixtures, i.e. those rich in long-chain PS esters, had the lower ability to impair CH micellarization. ConclusionsDifferent forms of PS have a different ability to impair CH micellarization. This ability depends on the transfer efficiency of PS from the food matrix to the micelle, which in turn depends on the melting point and the hydrophobicity of PS and on the delivery food matrix.

Purpose Vitamin E (VE) is essential for human health and may play a role in the aetiology of cardiovascular diseases. However, its absorption efficiency is widely variable. This high interindividual variability is assumed to be due to both dietary and genetic factors. Several polymorphisms have been identified but existing studies have so far focused on single SNPs that only explained a minor fraction of the variability of such a complex phenotype. This study thus aimed to identify a combination of SNPs that could explain a significant part of the variability in VE bioavailability. Methods Thirty-eight healthy male volunteers consumed a meal containing a VE supplement (134 mg a-tocopheryl acetate). Volunteers were genotyped using whole-genome microarrays. a-tocopherol (TOL) concentration was measured in plasma chylomicrons (CM) isolated at regular time intervals over 8 h postprandially. The association of SNPs in or near candidate genes (59 genes representing 4475 SNPs) with the postprandial CM TOL response was assessed by partial least squares regression. Results The postprandial CM TOL response to the meal was highly variable (CV of 81%). Data obtained allowed us to generate a validated significant model (P=1.8.10-8) that included 28 SNPs in 11 genes (ABCA1, ABCG1, APOB, BET1, IRS1, LIPC, NAT2, PNLIP, SLC10A2, SREBF2, ZNF664). This model explained 82% of the variance and allowed us to accurately predict a subject’s VE absorption (Spearman Rho=85% between the measured and predicted VE response). For all these SNPs, univariate analysis showed that subjects who bore different genotypes exhibited a significantly different VE absorption. Conclusions The ability to respond to VE appears to be at least in part genetically determined. A combination of SNPs in 11 genes related to both VE and CM metabolism can explain a large part of the variability in VE absorption in males. These results could allow a better design of future clinical trials aiming at studying the association of VE supplementation with the prevention of cardiovascular diseases.

International audience; The intake of tomatoes and tomato products, which constitute the main dietary source of the red pigment Lycopene (LYC), has been associated with a reduced risk of prostate cancer and cardiovascular disease, suggesting a protective role of this carotenoid. However, LYC bioavailability displays high interindividual variability. This variability may lead to varying biological effects following LYC consumption. Based on recent results obtained with two other carotenoids, we assumed that this variability was due, at least in part, to several single nucleotide polymorphisms (SNPs) in genes involved in LYC and lipid metabolism. Thus, we aimed at identifying a combination of SNPs significantly associated with the variability in LYC bioavailability. In a postprandial study, 33 healthy male volunteers consumed a test meal containing 100 g tomato puree, which provided 9.7 mg all-trans LYC. LYC concentrations were measured in plasma chylomicrons (CM) isolated at regular time intervals over 8 h postprandially. For the study 1885 SNPs in 49 candidate genes, i.e., genes assumed to play a role in LYC bioavailability, were selected. Multivariate statistical analysis (partial least squares regression) was used to identify and validate the combination of SNPs most closely associated with postprandial CM LYC response. The postprandial CM LYC response to the meal was notably variable with a CV of 70%. A significant (P.-0.037) and validated partial least squares regression model, which included 28 SNPs in 16 genes, explained 72% of the variance in the postprandial CM LYC response. The postprandial CM LYC response was also positively correlated to fasting plasma LYC concentrations (r=0.37, P< 0.05). The ability to respond to LYC is explained, at least partly, by a combination of 28 SNPs in 16 genes. Interindividual variability in bioavailability apparently affects the long-term blood LYC status, which could ultimately modulate the biological response following LYC supplementation.

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International audience; Both vitamin E (VE) consumption and blood VE status have been negatively associated with the incidence of degenerative diseases and some cancers. However, the response to VE supplementation is very variable among individuals. This could be due to interindividual variability in VE bioavailability, due, at least partly, to genetic variations in genes involved in VE metabolism. Thus, the main objective was to identify single nucleotide polymorphisms (SNPs) that may be involved in the interindividual variability in alpha-tocopherol (TOL) bioavailability. The postprandial chylomicron (CM) TOL response (area under the curve of the postprandial CM TOL concentration) to a TOL-rich meal was highly variable (coefficient of variation=81%; n=38). This response was positively correlated with the fasting plasma TOL concentration (r=0.5, p=0.004). A significant (p=1.8x10(-8)) partial least-squares regression model, which included 28 SNPs in 11 genes, explained 82% of this response. First evidence that the interindividual variability in TOL bioavailability is, at least partly, modulated by a combination of SNPs. TOL bioavailability is, at least partly, modulated by genetic variations that can affect long-term TOL status. This allows us to propose a new hypothesis that links the biological response to VE supplementation with one's individual genetic characteristics.

International audience; The interactions occurring at the intestinal level between the fat-soluble vitamins A, D, E and K (FSVs) are poorly documented. We first determined each FSV absorption profile along the duodenal-colonic axis of mouse intestine to clarify their respective absorption sites. We then investigated the interactions between FSVs during their uptake by Caco-2 cells. Our data show that vitamin A was mostly absorbed in the mouse proximal intestine, while vitamin D was absorbed in the median intestine, and vitamin E and K in the distal intestine. Significant competitive interactions for uptake were then elucidated among vitamin D, E and K, supporting the hypothesis of common absorption pathways. Vitamin A also significantly decreased the uptake of the other FSVs but, conversely, its uptake was not impaired by vitamins D and K and even promoted by vitamin E. These results should be taken into account, especially for supplement formulation, to optimise FSV absorption.

Background: Lutein accumulates in the macula and brain, where it is assumed to play physiologic roles. The bioavailability of lutein is assumed to display a high interindividual variability that has been hypothesized to be attributable, at least partly, to genetic polymorphisms. Objectives: We characterized the interindividual variability in lutein bioavailability in humans, assessed the relation between this variability and the fasting blood lutein concentration, and identified single nucleotide polymorphisms (SNPs) involved in this phenomenon. Design: In a randomized, 2-way crossover study, 39 healthy men consumed a meal that contained a lutein supplement or the same meal for which lutein was provided through a tomato puree. The lutein concentration was measured in plasma chylomicrons isolated at regular time intervals over 8 h postprandially. Multivariate statistical analyses were used to identify a combination of SNPs associated with the postprandial chylomicron lutein response (0‐8-h area under the curve). A total of 1785 SNPs in 51 candidate genes were selected. Results: Postprandial chylomicron lutein responses to meals were very variable (CVof 75% and 137% for the lutein-supplement meal and the meal with tomato-sourced lutein, respectively). Postprandial chylomicron lutein responses measured after the 2 meals were positively correlated (r = 0.68, P , 0.0001) and positively correlated to the fasting plasma lutein concentration (r = 0.51, P , 0.005 for the lutein-supplement‐containing meal). A significant (P = 1.9 3 10 24 ) and validated partial least-squares regression model, which included 29 SNPs in 15 genes, explained most of the variance in the postprandial chylomicron lutein response. Conclusions: The ability to respond to lutein appears to be, at least in part, genetically determined. The ability is explained, in large part, by a combination of SNPs in 15 genes related to both lutein and chylomicron metabolism. Finally, our results suggest that the ability to respond to lutein and blood lutein status are related. This trial was registered at clinicaltrials.gov as NCT02100774. Am J Clin Nutr doi: 10.3945/ajcn.114.085720.

International audience; Food fortification is a strategy to overcome vitamin A deficiency in developing countries. Our aim was to investigate the involvement of the bovine milk protein beta-lactoglobulin (beta-Lg), a potential retinoid carrier, in vitamin A absorption. In vivo experiments were conducted by force-feeding mice with retinol or beta-carotene associated with either beta-Lg or oil-in-water emulsion, with subsequent determination of both vitamin A intestinal mucosa and plasma contents. Caco-2 cells were then used to investigate the mechanisms of vitamin A uptake when delivered by either beta-Lg or mixed micelles. We showed that beta-Lg was as efficient as emulsion to promote beta-carotene, but not retinol, absorption in mice. Similar results were obtained in vitro. Interestingly, an inhibitor of the Scavenger Receptor Class B Type I significantly decreased the uptake of micellar beta-carotene but not that of beta-carotene bound to beta-Lg. Overall, we showed that beta-Lg would be a good vector for beta-carotene food fortification.

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International audience; We have recently shown that vitamin D-3 (cholecalciferol) absorption is not a simple passive diffusion but involves cholesterol transporters. As free fatty acids (FAs) modulate cholesterol intestinal absorption and metabolism, we hypothesized that FAs may also interact with vitamin D absorption. Effects of FAs were evaluated at different levels of cholecalciferol intestinal absorption. First, the physicochemical properties of micelles formed with different FAs were analyzed. The micelles were then administered to human Caco-2 cells in culture to evaluate FA effects on (i) cholecalciferol uptake and basolateral efflux and (ii) the regulation of genes coding proteins involved in lipid absorption process. Micellar electric charge was correlated with both FA chain length and degree of unsaturation. Long-chain FAs at 500 mu M in mixed micelles decreased cholecalciferol uptake in Caco-2 cells. This decrease was annihilated as soon as the long-chain FAs were mixed with other FAs. Oleic acid significantly improved cholecalciferol basolateral efflux compared to other FAs. These results were partly explained by a modulation of genes coding for lipid transport proteins such as Niemann-pick C1-like 1 and scavenger receptor class B type I. The data reported here show for the first time that FAs can interact with cholecalciferol intestinal absorption at different key steps of the absorption process. Cholecalciferol intestinal absorption may thus be optimized according to oil FA composition. (c) 2013 Elsevier Inc. All rights reserved.

The xanthophylls lutein and zeaxanthin probably play a role in visual function and may participate in the prevention of age-related eye diseases. Although a minimum amount of TAG is required for an optimal bioavailability of these carotenoids, the effect of the type of TAG fatty acids (FA) is less clear. The aim was to assess the effect of the type of TAG FA on bioavailability of these xanthophylls. A total of three complementary models were used: anin vitrodigestion model to study bioaccessibility, Caco-2 cells to study uptake efficiency and orally administered rats to studyin vivobioavailability. Results showed that lutein and zeaxanthin bioaccessibility was greater (about 20–30 %, PP

International audience; Consumption of phytosterols is a nutritional strategy to reduce cholesterol absorption, but the efficacy of various phytosterol intake modalities remains uncertain. The main objective was to investigate the effects of phytosterol esters (PE) provided either as a spread (dispersed in fat) during a mixed meal or as a minidrink (micro-dispersed in liquid form) after a meal. In a randomized, single-blinded crossover design, 12 healthy intubated volunteers tested three different liquid meal sequences with and without PE. The liquid meal (500 mL, Fortisip) contained an oral dose (80 mg) of deuterium-enriched cholesterol (D7C). The intubation was stopped at 240 min, and the fate of sterols was determined in the different phases of duodenal content samples as function of time. A second solid fat-containing meal without sterols was consumed at 270 min. D7C was quantified in chylomicrons and plasma for 8 h. The conditions tested were as follows: (1) no PE added (control), (2) PE in a spread added into a liquid meal (PE-spread meal) and (3) PE given 30 min after a liquid meal as 100-g yoghurt drink (PE-minidrink meal). Addition of PE decreased the incorporation of cholesterol into the duodenum aqueous phase including micelles. PE added as a spread or as a minidrink significantly and comparably lowered meal cholesterol occurrence in chylomicrons (-40 % for PE-spread and -54 % for PE-minidrink, p < 0.0001) compared with the control meal. PE either dispersed in fat during a meal or micro-dispersed in a liquid form after a meal resulted in a markedly reduced occurrence of meal-derived cholesterol in the circulation at a comparable extent.

International audience; Scope: Adequate vitamin D status is necessary and beneficial for health, although deficiency and insufficiency are very common. As cholecalciferol (vitamin D3) structure is close to cholesterol structure, we hypothesized that phytosterols, frequently used to decrease cholesterol, intestinal absorption and consequently to reduce hypercholesterolemia, may also interact with cholecalciferol absorption. Methods and results: β-Sitosterol effect on cholecalciferol postprandial response was first assessed in mice. We then evaluated the effect of different sterols on (i) cholecalciferol micellar incorporation, (ii) cholecalciferol apical uptake and (iii) basolateral efflux in vitro or ex vivo. In mice, cholecalciferol bioavailability was 15-fold lower in the presence of β-sitosterol (p

International audience; Phytosterols (plant sterols and stanols) can lower intestinal cholesterol absorption, but the complex dynamics of the lipid digestion process in the presence of phytosterol esters (PEs) are not fully understood. We performed a clinical experiment in intubated healthy subjects to study the time course of changes in the distribution of all lipid moieties present in duodenal phases during 4 h of digestion of meals with 3.2 g PE (PE meal) or without (control meal) PE. In vitro experiments under simulated gastrointestinal conditions were also performed. The addition of PE did not alter triglyceride (TG) hydrolysis in the duodenum or subsequent chylomicron TG occurrence in the circulation. In contrast, cholesterol accumulation in the duodenum aqueous phase was markedly reduced in the presence of PE (-32%, P < 0.10). In vitro experiments confirmed that PE reduces cholesterol transfer into the aqueous phase. The addition of PE resulted in a markedly reduced presence of meal-derived hepta-deuterated cholesterol in the circulation, i.e., in chylomicrons (-43%, PE meal vs. control; P < 0.0001) and plasma (-54%, PE meal vs. control; P < 0.0001). The present data show that addition of PE to a meal does not alter TG hydrolysis but displaces cholesterol from the intestinal aqueous phase and lowers chylomicron cholesterol occurrence in humans

International audience; Scope: It is assumed that vitamin D is absorbed by passive diffusion. However, since cholecalciferol (vitamin D(3) ) and cholesterol display similar structures, we hypothesized that common absorption pathways may exist. Methods and results: Cholecalciferol apical transport was first examined in human Caco-2 and transfected Human embryonic kidney (HEK) cells. Cholecalciferol uptake was then valuated ex vivo and in vivo, using either wild-type mice, mice overexpressing Scavenger Receptor class B type I (SR-BI) at the intestinal level or mice treated or not with ezetimibe. Cholecalciferol uptake was concentration-, temperature- and direction-dependent, and was significantly impaired by a co-incubation with cholesterol or tocopherol in Caco-2 cells. Moreover Block Lipid Transport-1 (SR-BI inhibitor) and ezetimibe glucuronide (Niemann-Pick C1 Like 1 inhibitor) significantly decreased cholecalciferol transport. Transfection of HEK cells with SR-BI, Cluster Determinant 36 and Niemann-Pick C1 Like 1 significantly enhanced vitamin D uptake, which was significantly decreased by the addition of Block Lipid Transport-1, sulfo-N-succinimidyl oleate (Cluster Determinant 36 inhibitor) or ezetimibe glucuronide, respectively. Similar results were obtained in mouse intestinal explants. In vivo, cholecalciferol uptake in proximal intestinal fragments was 60% higher in mice overexpressing SR-BI than in wild-type mice (p

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