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      Vitamin E Bioavailability: Mechanisms of Intestinal Absorption in the Spotlight

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          Abstract

          Vitamin E is an essential fat-soluble micronutrient whose effects on human health can be attributed to both antioxidant and non-antioxidant properties. A growing number of studies aim to promote vitamin E bioavailability in foods. It is thus of major interest to gain deeper insight into the mechanisms of vitamin E absorption, which remain only partly understood. It was long assumed that vitamin E was absorbed by passive diffusion, but recent data has shown that this process is actually far more complex than previously thought. This review describes the fate of vitamin E in the human gastrointestinal lumen during digestion and focuses on the proteins involved in the intestinal membrane and cellular transport of vitamin E across the enterocyte. Special attention is also given to the factors modulating both vitamin E micellarization and absorption. Although these latest results significantly improve our understanding of vitamin E intestinal absorption, further studies are still needed to decipher the molecular mechanisms driving this multifaceted process.

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          Most cited references83

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          Niemann-Pick C1 Like 1 (NPC1L1) is the intestinal phytosterol and cholesterol transporter and a key modulator of whole-body cholesterol homeostasis.

          Niemann-Pick C1 Like 1 (NPC1L1) is a protein localized in jejunal enterocytes that is critical for intestinal cholesterol absorption. The uptake of intestinal phytosterols and cholesterol into absorptive enterocytes in the intestine is not fully defined on a molecular level, and the role of NPC1L1 in maintaining whole body cholesterol homeostasis is not known. NPC1L1 null mice had substantially reduced intestinal uptake of cholesterol and sitosterol, with dramatically reduced plasma phytosterol levels. The NPC1L1 null mice were completely resistant to diet-induced hypercholesterolemia, with plasma lipoprotein and hepatic cholesterol profiles similar to those of wild type mice treated with the cholesterol absorption inhibitor ezetimibe. Cholesterol/cholate feeding resulted in down-regulation of intestinal NPC1L1 mRNA expression in wild type mice. NPC1L1 deficiency resulted in up-regulation of intestinal hydroxymethylglutaryl-CoA synthase mRNA and an increase in intestinal cholesterol synthesis, down-regulation of ABCA1 mRNA, and no change in ABCG5 and ABCG8 mRNA expression. NPC1L1 is required for intestinal uptake of both cholesterol and phytosterols and plays a major role in cholesterol homeostasis. Thus, NPC1L1 may be a useful drug target for the treatment of hypercholesterolemia and sitosterolemia.
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            Bioaccessibility of carotenoids and vitamin E from their main dietary sources.

            Vitamin E and carotenoids are fat-soluble microconstituents that may exert beneficial effects in humans, including protection against cancer, cardiovascular diseases, and age-related eye diseases. Their bioavailability is influenced by various factors including food matrix, formulation, and food processing. Since human studies are labor-intensive, time-consuming, and expensive, the in vitro model used in this study is increasingly being used to estimate bioaccessibility of these microconstituents. However, the ability of this model to predict bioavailability in a healthy human population has not yet been verified. The first aim of this study was to validate this model by comparing model-derived bioaccessibility data with (i) human-derived bioaccessibility data and (ii) published mean bioavailability data reported in studies involving healthy humans. The second aim was to use it to measure alpha- and gamma-tocopherol, beta-carotene, lycopene, and lutein bioaccessibility from their main dietary sources. Bioaccessibility as assessed with the in vitro model was well correlated with human-derived bioaccessibility values (r = 0.90, p beta-carotene and alpha-carotene > lycopene and alpha-tocopherol generally > gamma-tocopherol), (ii) food matrix, and (iii) food processing.
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              The cholesterol absorption inhibitor ezetimibe acts by blocking the sterol-induced internalization of NPC1L1.

              Niemann-Pick C1-like 1 (NPC1L1) is a polytopic transmembrane protein that plays a critical role in cholesterol absorption. Ezetimibe, a hypocholesterolemic drug, has been reported to bind NPC1L1 and block cholesterol absorption. However, the molecular mechanism of NPC1L1-mediated cholesterol uptake and how ezetimibe inhibits this process are poorly defined. Here we find that cholesterol specifically promotes the internalization of NPC1L1 and that this process requires microfilaments and the clathrin/AP2 complex. Blocking NPC1L1 endocytosis dramatically decreases cholesterol internalization, indicating that NPC1L1 mediates cholesterol uptake via its vesicular endocytosis. Ezetimibe prevents NPC1L1 from incorporating into clathrin-coated vesicles and thus inhibits cholesterol uptake. Together, our data suggest a model wherein cholesterol is internalized into cells with NPC1L1 through clathrin/AP2-mediated endocytosis and ezetimibe inhibits cholesterol absorption by blocking the internalization of NPC1L1.
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                Author and article information

                Journal
                Antioxidants (Basel)
                Antioxidants (Basel)
                antioxidants
                Antioxidants
                MDPI
                2076-3921
                22 November 2017
                December 2017
                : 6
                : 4
                : 95
                Affiliations
                Aix Marseille University, INRA, INSERM, C2VN, 13005 Marseille, France; Emmanuelle.Reboul@ 123456univ-amu.fr ; Tel.: +33-049-1324-278
                Author information
                https://orcid.org/0000-0002-4576-1992
                Article
                antioxidants-06-00095
                10.3390/antiox6040095
                5745505
                29165370
                a5c93b90-309d-458d-a8dc-fe373442c8fd
                © 2017 by the author.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 31 October 2017
                : 16 November 2017
                Categories
                Review

                tocopherol,intestine,mixed micelles,dietary lipids,food matrix,membrane transporters,uptake,enterocytes,chylomicrons,hdl,fat-soluble vitamins

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