Special Issue "Vitamin A Update 2016"

A special issue of Nutrients (ISSN 2072-6643).

Deadline for manuscript submissions: closed (31 October 2016).

Special Issue Editor

Prof. Dr. Maija H. Zile
E-Mail Website
Guest Editor
Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824, USA

Special Issue Information

Dear Colleagues,

The requirement for proper vitamin A nutrition throughout the human life cycle is well established. Most of the functions of vitamin A (retinol) are attributable to its active form, retinoic acid (RA) and RA-linked gene transcription pathways regulating a multitude of cellular processes. In this Special Issue on vitamin A, the focus will be on topics in vitamin A area that have not been recently addressed, as well as on some recent discoveries regarding vitamin A metabolism and function. Among the topics covered will be the determination of vitamin A status, which is very important for providing proper nutritional guidelines, as well as for addressing health issues in world populations where vitamin A inadequacy still exists. Reliable methodology is crucial and particularly critical during gestation, so that adequate vitamin A supplementation can be implemented, reliable epidemiological studies conducted and educational approaches planned. Another review in this Special Issue will update the generation of vitamin A from its plant source pro-vitamins and will also address recent experimental findings regarding the vitamin A/beta-carotene and lipid interactions, pointing out some health-related concerns. Recent advances in metabolism and function of retinol and RA during vertebrate embryonic development will be the topic of another review, highlighting the identification of the crucial enzyme in the biogeneration of RA. This discovery has not only provided the missing regulatory link in the metabolic pathway to the active form of vitamin A, but has also opened up new avenues to study human birth defects that might be linked to errors in RA signaling. The important function of RA in the regulation of the immune system will be another topic addressed in this Special Issue. While the immune system in humans develops during gestation, hematopoiesis or the formation of blood, i.e., blood cells starts in the early embryo; these hematopoietic stem cells form new lineages during development, then expand to bone morrow where they remain after birth and during adulthood. This topic will also be covered in the Special Issue, as RA is one of the many signaling factors regulating hematopoiesis.

The Editors of Nutrients extend an invitation to scientists to submit original research or reviews on any of the above topics for this Special Issue on vitamin A.

Dr. Maija H. Zile
Guest Editor

Manuscript Submission Information

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Keywords

  • Vitamin A, retinol
  • Retinoic acid (RA), vitamin A active form at gene level
  • Carotenoids, beta-carotene, provitamins A
  • Vitamin A biosynthesis
  • Assessment of vitamin A status
  • Interventions to prevent vitamin A deficiency in populations at risk  
  • Vitamin A deficiency and infectious diseases in populations at risk
  • RA and the immune system
  • RA regulation of hematopoiesis
  • Enzymes in RA biosynthesis
  • Birth defects linked to errors in retinoic acid signaling

Published Papers (15 papers)

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Editorial

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Open AccessEditorial
We Need Studies of the Mortality Effect of Vitamin A Supplementation, Not Surveys of Vitamin A Deficiency
Nutrients 2017, 9(3), 280; https://doi.org/10.3390/nu9030280 - 15 Mar 2017
Cited by 1
Abstract
It is usually acknowledged that high-dose vitamin A supplementation (VAS) provides no sustained improvement in vitamin A status, and that the effect of VAS on mortality is more likely linked to its immunomodulating effects. Nonetheless, it is widely assumed that we can deduce [...] Read more.
It is usually acknowledged that high-dose vitamin A supplementation (VAS) provides no sustained improvement in vitamin A status, and that the effect of VAS on mortality is more likely linked to its immunomodulating effects. Nonetheless, it is widely assumed that we can deduce something about the need for continuing or stopping VAS programs based on studies of the biochemical prevalence of vitamin A deficiency (VAD). This is no longer a tenable assumption. The justification for using VAS is to reduce child mortality, but there is now doubt that VAS has any effect on overall child mortality. What we need now are not surveys of VAD, but proper randomized trials to evaluate whether VAS has beneficial effects on overall child survival. Full article
(This article belongs to the Special Issue Vitamin A Update 2016)
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Research

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Open AccessArticle
‘Dose-to-Mother’ Deuterium Oxide Dilution Technique: An Accurate Strategy to Measure Vitamin A Intake in Breastfed Infants
Nutrients 2017, 9(2), 169; https://doi.org/10.3390/nu9020169 - 21 Feb 2017
Cited by 6
Abstract
In Mexico, infants (0–2 years old) show the highest prevalence of vitamin A deficiency (VAD), measured by serum retinol concentrations. Thus, we consider that low vitamin A (VA) intake through breast milk (BM) combined with poor weaning practices are the main factors that [...] Read more.
In Mexico, infants (0–2 years old) show the highest prevalence of vitamin A deficiency (VAD), measured by serum retinol concentrations. Thus, we consider that low vitamin A (VA) intake through breast milk (BM) combined with poor weaning practices are the main factors that contribute to VAD in this group. We combined the assessment of VA status in lactating women using BM retinol and a stable isotope ‘dose-to-mother’ technique to measure BM production in women from urban and agricultural areas. Infants’ mean BM intake was 758 ± 185 mL, and no difference was observed between both areas (p = 0.067). Mean BM retinol concentration was 1.09 μmol/L, which was significantly lower for the agricultural area (p = 0.028). Based on BM retinol concentration, 57% of women were VAD; although this prevalence fell to 16% when based on fat content. Regardless of the VA biomarker used here, infants from the urban and agricultural areas cover only 66% and 49% of their dietary adequate intake from BM, respectively (p = 0.054). Our data indicate that VAD is still a public health concern in Mexico. Adopting both methods to assess VA transfer from the mother to the breastfed child offers an innovative approach towards the nutritional assessment of vulnerable groups. Full article
(This article belongs to the Special Issue Vitamin A Update 2016)
Open AccessArticle
Low-Density Lipoprotein Receptor Contributes to β-Carotene Uptake in the Maternal Liver
Nutrients 2016, 8(12), 765; https://doi.org/10.3390/nu8120765 - 29 Nov 2016
Cited by 4
Abstract
Vitamin A regulates many essential mammalian biological processes, including embryonic development. β-carotene is the main source of vitamin A in the human diet. Once ingested, it is packaged into lipoproteins, predominantly low-density lipoproteins (LDL), and transported to different sites within the body, including [...] Read more.
Vitamin A regulates many essential mammalian biological processes, including embryonic development. β-carotene is the main source of vitamin A in the human diet. Once ingested, it is packaged into lipoproteins, predominantly low-density lipoproteins (LDL), and transported to different sites within the body, including the liver and developing tissues, where it can either be stored or metabolized to retinoids (vitamin A and its derivatives). The molecular mechanisms of β-carotene uptake by the liver or developing tissues remain elusive. Here, we investigated the role of the LDL receptor (LDLr) in β-carotene uptake by maternal liver, placenta and embryo. We administered a single dose of β-carotene to Ldlr+/− and Ldlr−/− pregnant mice via intraperitoneal injection at mid-gestation and monitored the changes in β-carotene content among maternal lipoproteins and the liver, as well as the accumulation of β-carotene in the placental–fetal unit. We showed an abnormal β-carotene distribution among serum lipoproteins and reduced hepatic β-carotene uptake in Ldlr−/− dams. These data strongly imply that LDLr significantly contributes to β-carotene uptake in the adult mouse liver. In contrast, LDLr does not seem to mediate acquisition of β-carotene by the placental–fetal unit. Full article
(This article belongs to the Special Issue Vitamin A Update 2016)
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Open AccessArticle
Serum Retinol Levels in Pregnant Adolescents and Their Relationship with Habitual Food Intake, Infection and Obstetric, Nutritional and Socioeconomic Variables
Nutrients 2016, 8(11), 669; https://doi.org/10.3390/nu8110669 - 25 Oct 2016
Cited by 7
Abstract
Globally, vitamin A deficiency (VAD) affects about 19.1 million pregnant women. Its occurrence is classically associated with inadequate food intake and may also be associated with socioeconomic factors and the presence of infection. The aim of this study was to determine the factors [...] Read more.
Globally, vitamin A deficiency (VAD) affects about 19.1 million pregnant women. Its occurrence is classically associated with inadequate food intake and may also be associated with socioeconomic factors and the presence of infection. The aim of this study was to determine the factors related to serum retinol levels among pregnant teenagers. The sample consisted of 89 pregnant adolescents, from whom socioeconomic, obstetric, anthropometric, and food consumption data were collected. Serum concentrations of retinol and the supposed presence of infection were determined by high-performance liquid chromatography and C-reactive protein quantification, respectively. The serum retinol concentrations were classified according to the criteria of the World Health Organization. We adopted a 5% significance level for all statistical tests. Serum retinol levels were significantly and positively associated with sanitation (p = 0.008) and pre-gestational nutritional status (p = 0.002), and negatively with the trimester (p = 0.001). The appropriate sanitation conditions and pre-pregnancy body mass index (BMI) were shown to have a protective effect against VAD. Conversely, serum retinol levels were reduced with trimester progression, favoring VAD occurrence. Full article
(This article belongs to the Special Issue Vitamin A Update 2016)
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Open AccessArticle
Serum Retinol Concentrations, Race, and Socioeconomic Status in of Women of Childbearing Age in the United States
Nutrients 2016, 8(8), 508; https://doi.org/10.3390/nu8080508 - 19 Aug 2016
Cited by 9
Abstract
Background: Vitamin A is an essential nutrient during pregnancy and throughout the lifecycle due to its role in the development of critical organ systems. Because maternal tissue is progressively depleted of vitamin A to supply fetal demands, women who become pregnant while possessing [...] Read more.
Background: Vitamin A is an essential nutrient during pregnancy and throughout the lifecycle due to its role in the development of critical organ systems. Because maternal tissue is progressively depleted of vitamin A to supply fetal demands, women who become pregnant while possessing marginal vitamin A reserves are at increased risk of vitamin A inadequacy as pregnancy progresses. Few studies have assessed the relationship between socioeconomic factors and retinol status in women of childbearing age. Methods: We used the National Health and Nutrition Examination Survey (NHANES) to assess the relationship between serum retinol concentrations and socioeconomic factors in women of childbearing age. Women 14–45 years of age (n = 3170) from NHANES cycles 2003–2004 and 2005–2006 were included. Serum retinol concentrations were divided into categories according to World Health Organization criteria. All statistical procedures accounted for the weighted data and complex design of the NHANES sample. A p-value of < 0.05 was considered statistically significant. Results: The poverty score and race were significantly associated with vitamin A status after adjustment for confounders. Odds of retinol concentrations of <1.05 µmol/L were 1.85 times higher for those of lower socioeconomic status when compared to those of higher status (95% CI: 1.12–3.03, p = 0.02), and 3.1 times higher for non-Hispanic blacks when compared to non-Hispanic whites (95% CI: 1.50–6.41, p = 0.002). Dietary intakes of retinol activity equivalents were significantly lower in groups with higher poverty scores (p = 0.004). Conclusion There appear to be disparities in serum vitamin A levels in women of childbearing age related to income and race in the United States. Full article
(This article belongs to the Special Issue Vitamin A Update 2016)
Open AccessArticle
9-cis β-Carotene Increased Cholesterol Efflux to HDL in Macrophages
Nutrients 2016, 8(7), 435; https://doi.org/10.3390/nu8070435 - 19 Jul 2016
Cited by 16
Abstract
Cholesterol efflux from macrophages is a key process in reverse cholesterol transport and, therefore, might inhibit atherogenesis. 9-cis-β-carotene (9-cis-βc) is a precursor for 9-cis-retinoic-acid (9-cis-RA), which regulates macrophage cholesterol efflux. Our objective was to assess [...] Read more.
Cholesterol efflux from macrophages is a key process in reverse cholesterol transport and, therefore, might inhibit atherogenesis. 9-cis-β-carotene (9-cis-βc) is a precursor for 9-cis-retinoic-acid (9-cis-RA), which regulates macrophage cholesterol efflux. Our objective was to assess whether 9-cis-βc increases macrophage cholesterol efflux and induces the expression of cholesterol transporters. Enrichment of a mouse diet with βc from the alga Dunaliella led to βc accumulation in peritoneal macrophages. 9-cis-βc increased the mRNA levels of CYP26B1, an enzyme that regulates RA cellular levels, indicating the formation of RA from βc in RAW264.7 macrophages. Furthermore, 9-cis-βc, as well as all-trans-βc, significantly increased cholesterol efflux to high-density lipoprotein (HDL) by 50% in RAW264.7 macrophages. Likewise, food fortification with 9-cis-βc augmented cholesterol efflux from macrophages ex vivo. 9-cis-βc increased both the mRNA and protein levels of ABCA1 and apolipoprotein E (APOE) and the mRNA level of ABCG1. Our study shows, for the first time, that 9-cis-βc from the diet accumulates in peritoneal macrophages and increases cholesterol efflux to HDL. These effects might be ascribed to transcriptional induction of ABCA1, ABCG1, and APOE. These results highlight the beneficial effect of βc in inhibition of atherosclerosis by improving cholesterol efflux from macrophages. Full article
(This article belongs to the Special Issue Vitamin A Update 2016)
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Open AccessArticle
Evaluation of Palm Oil as a Suitable Vegetable Oil for Vitamin A Fortification Programs
Nutrients 2016, 8(6), 378; https://doi.org/10.3390/nu8060378 - 21 Jun 2016
Cited by 8
Abstract
Fortification programs are considered to be an effective strategy to mitigate vitamin A deficiency in populations at risk. Fortified vegetable oils rich in polyunsaturated fatty acids were shown to be prone to oxidation, leading to limited vitamin A stability. Thus, it was hypothesized [...] Read more.
Fortification programs are considered to be an effective strategy to mitigate vitamin A deficiency in populations at risk. Fortified vegetable oils rich in polyunsaturated fatty acids were shown to be prone to oxidation, leading to limited vitamin A stability. Thus, it was hypothesized that fortified oils consisting of mainly saturated fatty acids might enhance the stability of vitamin A. Mildly (peroxide value: 1.0 meq O2/kg) and highly (peroxide value: 7.5 meq O2/kg) oxidized palm oil was stored, after fortification with 60 International Units/g retinyl palmitate, in 0.5 L transparent polyethylene terephthalate bottles under cold fluorescent lighting (12 h/day) at 32 °C for 57 days. An increase of the peroxide value by 15 meq O2/kg, which was also reflected by a decrease of α-tocopherol congener by 15%–18%, was determined independent of the initial rancidity. The oxidative deterioration of the highly oxidized palm oil during storage was correlated with a significant 46% decline of the vitamin A content. However, household storage of mildly oxidized palm oil for two months did not induce any losses of vitamin A. Thus, mildly oxidized palm oil may be recommended for vitamin A fortification programs, when other sources of essential fatty acids are available. Full article
(This article belongs to the Special Issue Vitamin A Update 2016)
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Review

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Open AccessReview
Vitamin A Supplementation Programs and Country-Level Evidence of Vitamin A Deficiency
Nutrients 2017, 9(3), 190; https://doi.org/10.3390/nu9030190 - 24 Feb 2017
Cited by 40
Abstract
Vitamin A supplementation (VAS) programs targeted at children aged 6–59 months are implemented in many countries. By improving immune function, vitamin A (VA) reduces mortality associated with measles, diarrhea, and other illnesses. There is currently a debate regarding the relevance of VAS, but [...] Read more.
Vitamin A supplementation (VAS) programs targeted at children aged 6–59 months are implemented in many countries. By improving immune function, vitamin A (VA) reduces mortality associated with measles, diarrhea, and other illnesses. There is currently a debate regarding the relevance of VAS, but amidst the debate, researchers acknowledge that the majority of nationally-representative data on VA status is outdated. To address this data gap and contribute to the debate, we examined data from 82 countries implementing VAS programs, identified other VA programs, and assessed the recentness of national VA deficiency (VAD) data. We found that two-thirds of the countries explored either have no VAD data or data that were >10 years old (i.e., measured before 2006), which included twenty countries with VAS coverage ≥70%. Fifty-one VAS programs were implemented in parallel with at least one other VA intervention, and of these, 27 countries either had no VAD data or data collected in 2005 or earlier. To fill these gaps in VAD data, countries implementing VAS and other VA interventions should measure VA status in children at least every 10 years. At the same time, the coverage of VA interventions can also be measured. We identified three countries that have scaled down VAS, but given the lack of VA deficiency data, this would be a premature undertaking in most countries without appropriate status assessment. While the global debate about VAS is important, more attention should be directed towards individual countries where programmatic decisions are made. Full article
(This article belongs to the Special Issue Vitamin A Update 2016)
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Open AccessReview
Role of Vitamin A/Retinoic Acid in Regulation of Embryonic and Adult Hematopoiesis
Nutrients 2017, 9(2), 159; https://doi.org/10.3390/nu9020159 - 20 Feb 2017
Cited by 34
Abstract
Vitamin A is an essential micronutrient throughout life. Its physiologically active metabolite retinoic acid (RA), acting through nuclear retinoic acid receptors (RARs), is a potent regulator of patterning during embryonic development, as well as being necessary for adult tissue homeostasis. Vitamin A deficiency [...] Read more.
Vitamin A is an essential micronutrient throughout life. Its physiologically active metabolite retinoic acid (RA), acting through nuclear retinoic acid receptors (RARs), is a potent regulator of patterning during embryonic development, as well as being necessary for adult tissue homeostasis. Vitamin A deficiency during pregnancy increases risk of maternal night blindness and anemia and may be a cause of congenital malformations. Childhood Vitamin A deficiency can cause xerophthalmia, lower resistance to infection and increased risk of mortality. RA signaling appears to be essential for expression of genes involved in developmental hematopoiesis, regulating the endothelial/blood cells balance in the yolk sac, promoting the hemogenic program in the aorta-gonad-mesonephros area and stimulating eryrthropoiesis in fetal liver by activating the expression of erythropoietin. In adults, RA signaling regulates differentiation of granulocytes and enhances erythropoiesis. Vitamin A may facilitate iron absorption and metabolism to prevent anemia and plays a key role in mucosal immune responses, modulating the function of regulatory T cells. Furthermore, defective RA/RARα signaling is involved in the pathogenesis of acute promyelocytic leukemia due to a failure in differentiation of promyelocytes. This review focuses on the different roles played by vitamin A/RA signaling in physiological and pathological mouse hematopoiesis duddurring both, embryonic and adult life, and the consequences of vitamin A deficiency for the blood system. Full article
(This article belongs to the Special Issue Vitamin A Update 2016)
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Open AccessReview
Retinoic Acid and Its Role in Modulating Intestinal Innate Immunity
Nutrients 2017, 9(1), 68; https://doi.org/10.3390/nu9010068 - 13 Jan 2017
Cited by 25
Abstract
Vitamin A (VA) is amongst the most well characterized food-derived nutrients with diverse immune modulatory roles. Deficiency in dietary VA has not only been associated with immune dysfunctions in the gut, but also with several systemic immune disorders. In particular, VA metabolite all-trans [...] Read more.
Vitamin A (VA) is amongst the most well characterized food-derived nutrients with diverse immune modulatory roles. Deficiency in dietary VA has not only been associated with immune dysfunctions in the gut, but also with several systemic immune disorders. In particular, VA metabolite all-trans retinoic acid (atRA) has been shown to be crucial in inducing gut tropism in lymphocytes and modulating T helper differentiation. In addition to the widely recognized role in adaptive immunity, increasing evidence identifies atRA as an important modulator of innate immune cells, such as tolerogenic dendritic cells (DCs) and innate lymphoid cells (ILCs). Here, we focus on the role of retinoic acid in differentiation, trafficking and the functions of innate immune cells in health and inflammation associated disorders. Lastly, we discuss the potential involvement of atRA during the plausible crosstalk between DCs and ILCs. Full article
(This article belongs to the Special Issue Vitamin A Update 2016)
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Open AccessReview
Hepatic Retinyl Ester Hydrolases and the Mobilization of Retinyl Ester Stores
Nutrients 2017, 9(1), 13; https://doi.org/10.3390/nu9010013 - 27 Dec 2016
Cited by 6
Abstract
For mammals, vitamin A (retinol and metabolites) is an essential micronutrient that is required for the maintenance of life. Mammals cannot synthesize vitamin A but have to obtain it from their diet. Resorbed dietary vitamin A is stored in large quantities in the [...] Read more.
For mammals, vitamin A (retinol and metabolites) is an essential micronutrient that is required for the maintenance of life. Mammals cannot synthesize vitamin A but have to obtain it from their diet. Resorbed dietary vitamin A is stored in large quantities in the form of retinyl esters (REs) in cytosolic lipid droplets of cells to ensure a constant supply of the body. The largest quantities of REs are stored in the liver, comprising around 80% of the body’s total vitamin A content. These hepatic vitamin A stores are known to be mobilized under times of insufficient dietary vitamin A intake but also under pathological conditions such as chronic alcohol consumption and different forms of liver diseases. The mobilization of REs requires the activity of RE hydrolases. It is astounding that despite their physiological significance little is known about their identities as well as about factors or stimuli which lead to their activation and consequently to the mobilization of hepatic RE stores. In this review, we focus on the recent advances for the understanding of hepatic RE hydrolases and discuss pathological conditions which lead to the mobilization of hepatic RE stores. Full article
(This article belongs to the Special Issue Vitamin A Update 2016)
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Open AccessReview
Enzymatic Metabolism of Vitamin A in Developing Vertebrate Embryos
Nutrients 2016, 8(12), 812; https://doi.org/10.3390/nu8120812 - 15 Dec 2016
Cited by 17
Abstract
Embryonic development is orchestrated by a small number of signaling pathways, one of which is the retinoic acid (RA) signaling pathway. Vitamin A is essential for vertebrate embryonic development because it is the molecular precursor of the essential signaling molecule RA. The level [...] Read more.
Embryonic development is orchestrated by a small number of signaling pathways, one of which is the retinoic acid (RA) signaling pathway. Vitamin A is essential for vertebrate embryonic development because it is the molecular precursor of the essential signaling molecule RA. The level and distribution of RA signaling within a developing embryo must be tightly regulated; too much, or too little, or abnormal distribution, all disrupt embryonic development. Precise regulation of RA signaling during embryogenesis is achieved by proteins involved in vitamin A metabolism, retinoid transport, nuclear signaling, and RA catabolism. The reversible first step in conversion of the precursor vitamin A to the active retinoid RA is mediated by retinol dehydrogenase 10 (RDH10) and dehydrogenase/reductase (SDR family) member 3 (DHRS3), two related membrane-bound proteins that functionally activate each other to mediate the interconversion of retinol and retinal. Alcohol dehydrogenase (ADH) enzymes do not contribute to RA production under normal conditions during embryogenesis. Genes involved in vitamin A metabolism and RA catabolism are expressed in tissue-specific patterns and are subject to feedback regulation. Mutations in genes encoding these proteins disrupt morphogenesis of many systems in a developing embryo. Together these observations demonstrate the importance of vitamin A metabolism in regulating RA signaling during embryonic development in vertebrates. Full article
(This article belongs to the Special Issue Vitamin A Update 2016)
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Open AccessReview
Retinol Dehydrogenases Regulate Vitamin A Metabolism for Visual Function
Nutrients 2016, 8(11), 746; https://doi.org/10.3390/nu8110746 - 22 Nov 2016
Cited by 12
Abstract
The visual system produces visual chromophore, 11-cis-retinal from dietary vitamin A, all-trans-retinol making this vitamin essential for retinal health and function. These metabolic events are mediated by a sequential biochemical process called the visual cycle. Retinol dehydrogenases (RDHs) are [...] Read more.
The visual system produces visual chromophore, 11-cis-retinal from dietary vitamin A, all-trans-retinol making this vitamin essential for retinal health and function. These metabolic events are mediated by a sequential biochemical process called the visual cycle. Retinol dehydrogenases (RDHs) are responsible for two reactions in the visual cycle performed in retinal pigmented epithelial (RPE) cells, photoreceptor cells and Müller cells in the retina. RDHs in the RPE function as 11-cis-RDHs, which oxidize 11-cis-retinol to 11-cis-retinal in vivo. RDHs in rod photoreceptor cells in the retina work as all-trans-RDHs, which reduce all-trans-retinal to all-trans-retinol. Dysfunction of RDHs can cause inherited retinal diseases in humans. To facilitate further understanding of human diseases, mouse models of RDHs-related diseases have been carefully examined and have revealed the physiological contribution of specific RDHs to visual cycle function and overall retinal health. Herein we describe the function of RDHs in the RPE and the retina, particularly in rod photoreceptor cells, their regulatory properties for retinoid homeostasis and future therapeutic strategy for treatment of retinal diseases. Full article
(This article belongs to the Special Issue Vitamin A Update 2016)
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Open AccessReview
Molecular Basis for Vitamin A Uptake and Storage in Vertebrates
Nutrients 2016, 8(11), 676; https://doi.org/10.3390/nu8110676 - 26 Oct 2016
Cited by 17
Abstract
The ability to store and distribute vitamin A inside the body is the main evolutionary adaptation that allows vertebrates to maintain retinoid functions during nutritional deficiencies and to acquire new metabolic pathways enabling light-independent production of 11-cis retinoids. These processes greatly depend [...] Read more.
The ability to store and distribute vitamin A inside the body is the main evolutionary adaptation that allows vertebrates to maintain retinoid functions during nutritional deficiencies and to acquire new metabolic pathways enabling light-independent production of 11-cis retinoids. These processes greatly depend on enzymes that esterify vitamin A as well as associated retinoid binding proteins. Although the significance of retinyl esters for vitamin A homeostasis is well established, until recently, the molecular basis for the retinol esterification enzymatic activity was unknown. In this review, we will look at retinoid absorption through the prism of current biochemical and structural studies on vitamin A esterifying enzymes. We describe molecular adaptations that enable retinoid storage and delineate mechanisms in which mutations found in selective proteins might influence vitamin A homeostasis in affected patients. Full article
(This article belongs to the Special Issue Vitamin A Update 2016)
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Open AccessReview
Retinoic Acid as a Modulator of T Cell Immunity
Nutrients 2016, 8(6), 349; https://doi.org/10.3390/nu8060349 - 13 Jun 2016
Cited by 33
Abstract
Vitamin A, a generic designation for an array of organic molecules that includes retinal, retinol and retinoic acid, is an essential nutrient needed in a wide array of aspects including the proper functioning of the visual system, maintenance of cell function and differentiation, [...] Read more.
Vitamin A, a generic designation for an array of organic molecules that includes retinal, retinol and retinoic acid, is an essential nutrient needed in a wide array of aspects including the proper functioning of the visual system, maintenance of cell function and differentiation, epithelial surface integrity, erythrocyte production, reproduction, and normal immune function. Vitamin A deficiency is one of the most common micronutrient deficiencies worldwide and is associated with defects in adaptive immunity. Reports from epidemiological studies, clinical trials and experimental studies have clearly demonstrated that vitamin A plays a central role in immunity and that its deficiency is the cause of broad immune alterations including decreased humoral and cellular responses, inadequate immune regulation, weak response to vaccines and poor lymphoid organ development. In this review, we will examine the role of vitamin A in immunity and focus on several aspects of T cell biology such as T helper cell differentiation, function and homing, as well as lymphoid organ development. Further, we will provide an overview of the effects of vitamin A deficiency in the adaptive immune responses and how retinoic acid, through its effect on T cells can fine-tune the balance between tolerance and immunity. Full article
(This article belongs to the Special Issue Vitamin A Update 2016)
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