Vitamin A deficiency during the perinatal period induces changes in vitamin A metabolism in the offspring. The regulation of intestinal vitamin A metabolism via ISX occurs only in male rats severely vitamin A-deficient.

PURPOSE: 1) To test the hypothesis of the existence of a perinatal vitamin A (VA) programming of VA metabolism and to better understand the intestinal regulation of VA metabolism. METHODS: Offspring from rats reared on a control (C) or a VA-deficient (D) diet from 6 weeks before mating until offspring weaning, i.e., 7 weeks after mating, were themselves reared on a C or D diet for 19 weeks, resulting in the following groups: C-C (parents fed C-offspring fed C), D-C, C-D and D-D. VA concentrations were measured in plasma and liver. ß-Carotene bioavailability and its intestinal conversion rate to VA, as well as vitamin D and E bioavailability, were assessed after gavages with these vitamins. Expression of genes involved in VA metabolism and transport was measured in intestine and liver. RESULTS: C-D and D-D had no detectable retinyl esters in their liver. Retinolemia, hepatic retinol concentrations and postprandial plasma retinol response to ß-carotene gavage were higher in D-C than in C-C. Intestinal expression of Isx was abolished in C-D and D-D and this was concomitant with a higher expression of Bco1, Scarb1, Cd36 and Lrat in males receiving a D diet as compared to those receiving a C diet. ß-Carotene, vitamin D and E bio-availabilities were lower in offspring receiving a D diet as compared to those receiving a C diet. CONCLUSION: A VA-deficient diet during the perinatal period modifies the metabolism of this vitamin in the offspring. Isx-mediated regulation of Bco1 and Scarb1 expression exists only in males severely deficient in this vitamin. Severe VA deficiency impairs ß-carotene and vitamin D and E bioavailability.

One-Step Extraction of Olive Phenols from Aqueous Solution Using ß-Cyclodextrin in the Solid State, a Simple Eco-Friendly Method Providing Photochemical Stability to the Extracts.

The extraction of phenolic compounds from olive mill wastes is important, not only to avoid environmental damages, but also because of the intrinsic value of those biophenols, well-known for their high antioxidant potential and health benefits. This study focuses on tyrosol (Tyr) and hydroxytyrosol (HT), two of the main phenolic compounds found in olive mill wastes. A new, simple, and eco-friendly extraction process for the removal of phenolic compounds from aqueous solutions using native ß-cyclodextrin (ß-CD) in the solid state has been developed. Several ß-CD/biophenol molar ratios and biophenol concentrations were investigated, in order to maintain ß-CD mostly in the solid state while optimizing the extraction yield and the loading capacity of the sorbent. The extraction efficiencies of Tyr and HT were up to 61%, with a total solid recovery higher than 90% using an initial concentration of 100 mM biophenol and 10 molar equivalents of ß-CD. The photochemical stability of the complexes thus obtained was estimated from ∆E*ab curve vs. illumination time. The results obtained showed that the phenols encapsulated into solid ß-CD are protected against photodegradation. The powder obtained could be directly developed as a safe-grade food supplement. This simple eco-friendly process could be used for extracting valuable biophenols from olive mill wastewater.

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

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.

Vitamin E intestinal absorption: Regulation of membrane transport across the enterocyte.

Vitamin E is an essential molecule for our development and health. It has long been thought that it was absorbed and transported through cellular membranes by a passive diffusion process. However, data obtained during the past 15 years showed that its absorption is actually mediated, at least in part, by cholesterol membrane transporters including the scavenger receptor class B type I (SR-BI), CD36 molecule (CD36), NPC1-like transporter 1 (NPC1L1), and ATP-binding cassettes A1 and G1 (ABCA1 and ABCG1). This review focuses on the absorption process of vitamin E across the enterocyte. A special attention is given to the regulation of this process, including the possible competition with other fat-soluble micronutrients, and the modulation of transporter expressions. Overall, recent results noticeably increased the comprehension of vitamin E intestinal transport, but additional investigations are still required to fully appreciate the mechanisms governing vitamin E bioavailability. © 2018 IUBMB Life, 71(4):416-423, 2019.

Efficacy of two vitamin E formulations in patients with abetalipoproteinemia and chylomicron retention disease.

Abetalipoproteinemia (ABL) and chylomicron retention disease (CMRD) are extremely rare recessive forms of hypobetalipoproteinemia characterized by intestinal lipid malabsorption and severe vitamin E deficiency. Vitamin E is often supplemented in the form of fat-soluble vitamin E acetate, but fat malabsorption considerably limits correction of the deficiency. In this crossover study, we administered two different forms of vitamin E, tocofersolan (a water-soluble derivative of RRR-α-tocopherol) and α-tocopherol acetate, to three patients with ABL and four patients with CMRD. The aims of this study were to evaluate the intestinal absorption characteristics of tocofersolan versus α-tocopherol acetate by measuring the plasma concentrations of α-tocopherol over time after a single oral load and to compare efficacy by evaluating the ability of each formulation to restore vitamin E storage after 4 months of treatment. In patients with ABL, tocofersolan and α-tocopherol acetate bioavailabilities were extremely low (2.8% and 3.1%, respectively). In contrast, bioavailabilities were higher in patients with CMRD (tocofersolan, 24.7%; α-tocopherol acetate, 11.4%). Plasma concentrations of α-tocopherol at 4 months were not significantly different by formulation type in ABL or CMRD. This study provides new insights about vitamin E status in ABL and CMRD and suggests the potential of different formulations as treatment options.

A Combination of Single-Nucleotide Polymorphisms Is Associated with Interindividual Variability in Cholecalciferol Bioavailability in Healthy Men.

BACKGROUND: Most people require dietary vitamin 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 (in kg/m2) 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 × 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.

Micellar lipid composition affects micelle interaction with class B scavenger receptor extracellular loops.

Scavenger receptors (SRs) like cluster determinant 36 (CD36) and SR class B type I (SR-BI) play a debated role in lipid transport across the intestinal brush border membrane. We used surface plasmon resonance to analyze real-time interactions between the extracellular protein loops and various ligands ranging from single lipid molecules to mixed micelles. Micelles mimicking physiological structures were necessary for optimal binding to both the extracellular loop of CD36 (lCD36) and the extracellular loop of SR-BI (lSR-BI). Cholesterol, phospholipid, and fatty acid micellar content significantly modulated micelle binding to and dissociation from the transporters. In particular, high phospholipid micellar concentrations inhibited micelle binding to both receptors (-53.8 and -74.4% binding at 0.32 mM compared with 0.04 mM for lCD36 and lSR-BI, respectively, P < 0.05). The presence of fatty acids was crucial for micelle interactions with both proteins (94.4 and 81.3% binding with oleic acid for lCD36 and lSR-BI, respectively, P < 0.05) and fatty acid type substitution within the micelles was the component that most impacted micelle binding to the transporters. These effects were partly due to subsequent modifications in micellar size and surface electric charge, and could be correlated to micellar vitamin D uptake by Caco-2 cells. Our findings show for the first time that micellar lipid composition and micellar properties are key factors governing micelle interactions with SRs.

Intestinal scavenger receptors are involved in vitamin K1 absorption.

Vitamin K1 (phylloquinone) intestinal absorption is thought to be mediated by a carrier protein that still remains to be identified. Apical transport of vitamin K1 was examined using Caco-2 TC-7 cell monolayers as a model of human intestinal epithelium and in transfected HEK cells. Phylloquinone uptake was then measured ex vivo using mouse intestinal explants. Finally, vitamin K1 absorption was compared between wild-type mice and mice overexpressing scavenger receptor class B type I (SR-BI) in the intestine and mice deficient in cluster determinant 36 (CD36). Phylloquinone uptake by Caco-2 cells was saturable and was significantly impaired by co-incubation with α-tocopherol (and vice versa). Anti-human SR-BI antibodies and BLT1 (a chemical inhibitor of lipid transport via SR-BI) blocked up to 85% of vitamin K1 uptake. BLT1 also decreased phylloquinone apical efflux by ∼80%. Transfection of HEK cells with SR-BI and CD36 significantly enhanced vitamin K1 uptake, which was subsequently decreased by the addition of BLT1 or sulfo-N-succinimidyl oleate (CD36 inhibitor), respectively. Similar results were obtained in mouse intestinal explants. In vivo, the phylloquinone postprandial response was significantly higher, and the proximal intestine mucosa phylloquinone content 4 h after gavage was increased in mice overexpressing SR-BI compared with controls. Phylloquinone postprandial response was also significantly increased in CD36-deficient mice compared with wild-type mice, but their vitamin K1 intestinal content remained unchanged. Overall, the present data demonstrate for the first time that intestinal scavenger receptors participate in the absorption of dietary phylloquinone.

ABCG1 is involved in vitamin E efflux.

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 Abcgl-deficient mice, vitamin E concentration was reduced in plasma lipoproteins whereas most tissues displayed a higher vitamin E content compared to wild-type mice. α- and γ-tocopherol efflux was increased in CHO cells overexpressing human ABCG1 compared to control cells. Conversely, α- and γ- tocopherol efflux was decreased in ABCG1-knockdown human cells (Hep3B hepatocytes and THP-1 macro- phages). Interestingly, α- and γ-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.

Combination of legume proteins and arabinoxylans are efficient emulsifiers to promote vitamin E bioaccessibility during digestion.

The emulsification potential of plant-based emulsifiers, that is, pea (PPI) and lentil (LPI) proteins (4%), corn arabinoxylans (CAX, 1%), and legume protein-arabinoxylan mixtures (4% proteins + 0.15 or 0.9% CAX), was evaluated by assessing: the surface tension and potential of emulsifiers, emulsifier antinutritional contents, emulsion droplet size, emulsion physical stability, and vitamin E bioaccessibility from 10% oil-in-water emulsions. Tween 80 (2%) was used as a control. All emulsions presented small droplet sizes, both fresh and upon storage, except 4% LPI + 0.9% CAX emulsion that exhibited bigger droplet sizes (d(4,3) of approximately 18.76 µm vs 0.59 µm for the control) because of droplet bridging. Vitamin E bioaccessibility from emulsions stabilized with the combination of 4% PPI and either 0.15% or 0.9% CAX (28 ± 4.48% and 28.42 ± 3.87%, respectively) was not significantly different from that of emulsions stabilized with Tween 80 (43.56 ± 3.71%), whereas vitamin E bioaccessibility from emulsions stabilized with individual emulsifiers was significantly lower.