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Nutrients Jul 2022Vitamin A is a fat-soluble micronutrient necessary for the growth of healthy skin and hair. However, both too little and too much vitamin A has deleterious effects.... (Review)
Review
Vitamin A is a fat-soluble micronutrient necessary for the growth of healthy skin and hair. However, both too little and too much vitamin A has deleterious effects. Retinoic acid and retinal are the main active metabolites of vitamin A. Retinoic acid dose-dependently regulates hair follicle stem cells, influencing the functioning of the hair cycle, wound healing, and melanocyte stem cells. Retinoic acid also influences melanocyte differentiation and proliferation in a dose-dependent and temporal manner. Levels of retinoids decline when exposed to ultraviolet irradiation in the skin. Retinal is necessary for the phototransduction cascade that initiates melanogenesis but the source of that retinal is currently unknown. This review discusses new research on retinoids and their effects on the skin and hair.
Topics: Hair; Retinoids; Skin; Tretinoin; Vitamin A
PubMed: 35889909
DOI: 10.3390/nu14142952 -
Nature Communications Mar 2023Diabetic cardiomyopathy is a primary myocardial injury induced by diabetes with complex pathogenesis. In this study, we identify disordered cardiac retinol metabolism in...
Diabetic cardiomyopathy is a primary myocardial injury induced by diabetes with complex pathogenesis. In this study, we identify disordered cardiac retinol metabolism in type 2 diabetic male mice and patients characterized by retinol overload, all-trans retinoic acid deficiency. By supplementing type 2 diabetic male mice with retinol or all-trans retinoic acid, we demonstrate that both cardiac retinol overload and all-trans retinoic acid deficiency promote diabetic cardiomyopathy. Mechanistically, by constructing cardiomyocyte-specific conditional retinol dehydrogenase 10-knockout male mice and overexpressing retinol dehydrogenase 10 in male type 2 diabetic mice via adeno-associated virus, we verify that the reduction in cardiac retinol dehydrogenase 10 is the initiating factor for cardiac retinol metabolism disorder and results in diabetic cardiomyopathy through lipotoxicity and ferroptosis. Therefore, we suggest that the reduction of cardiac retinol dehydrogenase 10 and its mediated disorder of cardiac retinol metabolism is a new mechanism underlying diabetic cardiomyopathy.
Topics: Male; Animals; Mice; Diabetic Cardiomyopathies; Vitamin A; Diabetes Mellitus, Experimental; Metabolic Diseases; Tretinoin; Heart Diseases; Mice, Knockout; Myocytes, Cardiac; Diabetes Mellitus, Type 2
PubMed: 36864033
DOI: 10.1038/s41467-023-36837-x -
Ciencia & Saude Coletiva Mar 2019To evaluate the effect of vitamin A supplementation in postpartum infants and women on serum retinol levels and breast milk. The databases Medline, PubMed, Lilacs and...
To evaluate the effect of vitamin A supplementation in postpartum infants and women on serum retinol levels and breast milk. The databases Medline, PubMed, Lilacs and SciELO were consulted. The descriptors used were vitamin A, dietary supplement, child, postpartum period, infant and nutrition programs policies. Search found 7432 articles. After elimination of duplicity and application of eligibility criteria, 8 studies remained. All evaluated the effect of vitamin A supplementation on immediate postpartum, five studies used retinyl palmitate supplementation, one with retinyl palmitate and two did not specify the form of supplementation. Six studies evaluated colostrum and two included supplementation of children. It was found that supplementation in the puerperium increases the concentrations of serum retinol and breast milk, however, this result was in the short term and was relevant when the previous concentrations of the mother were low. When maternal serum concentrations are adequate, the retinol content in milk does not change, with little relevance for children. Further studies should be performed to evaluate the effect of megadoses supplementation on serum concentrations of children.
Topics: Colostrum; Dietary Supplements; Diterpenes; Female; Humans; Infant, Newborn; Milk, Human; Postpartum Period; Pregnancy; Retinyl Esters; Time Factors; Vitamin A; Vitamin A Deficiency
PubMed: 30892504
DOI: 10.1590/1413-81232018243.07112017 -
Nutrients Jan 2021Vitamin A is a fat-soluble vitamin that plays an important role in skin immunity. Deficiencies in Vitamin A have been linked to impaired immune response and increased... (Review)
Review
Vitamin A is a fat-soluble vitamin that plays an important role in skin immunity. Deficiencies in Vitamin A have been linked to impaired immune response and increased susceptibility to skin infections and inflammatory skin disease. This narrative review summarizes recent primary evidence that elucidates the role of vitamin A and its derivatives on innate immune regulators through mechanisms that promote skin immunity and sustain the skin microbiome.
Topics: Animals; Dermatitis; Humans; Immunity, Innate; Microbiota; Skin; Staphylococcus aureus; Tretinoin; Vitamin A; Vitamin A Deficiency
PubMed: 33494277
DOI: 10.3390/nu13020302 -
Biomedicine & Pharmacotherapy =... Aug 2023Vitamin A (retinol) is a lipid-soluble vitamin that acts as a precursor for several bioactive compounds, such as retinaldehyde (retinal) and isomers of retinoic acid....
Vitamin A (retinol) is a lipid-soluble vitamin that acts as a precursor for several bioactive compounds, such as retinaldehyde (retinal) and isomers of retinoic acid. Retinol and all-trans-retinoic acid (atRA) penetrate the blood-brain barrier and are reported to be neuroprotective in several animal models. We characterised the impact of retinol and its metabolites, all-trans-retinal (atRAL) and atRA, on ferroptosis-a programmed cell death caused by iron-dependent phospholipid peroxidation. Ferroptosis was induced by erastin, buthionine sulfoximine or RSL3 in neuronal and non-neuronal cell lines. We found that retinol, atRAL and atRA inhibited ferroptosis with a potency superior to α-tocopherol, the canonical anti-ferroptotic vitamin. In contrast, we found that antagonism of endogenous retinol with anhydroretinol sensitises ferroptosis induced in neuronal and non-neuronal cell lines. Retinol and its metabolites atRAL and atRA directly interdict lipid radicals in ferroptosis since these compounds displayed radical trapping properties in a cell-free assay. Vitamin A, therefore, complements other anti-ferroptotic vitamins, E and K; metabolites of vitamin A, or agents that alter their levels, may be potential therapeutics for diseases where ferroptosis is implicated.
Topics: Animals; Vitamin A; Ferroptosis; Lipid Peroxidation; Tretinoin; Vitamins; Retinaldehyde; Lipids
PubMed: 37236031
DOI: 10.1016/j.biopha.2023.114930 -
Methods in Enzymology 2020Generation of the autacoid all-trans-retinoic acid (ATRA) from retinol (vitamin A) relies on a complex metabolon that includes retinol binding-proteins and enzymes from...
Generation of the autacoid all-trans-retinoic acid (ATRA) from retinol (vitamin A) relies on a complex metabolon that includes retinol binding-proteins and enzymes from the short-chain dehydrogenase/reductase and aldehyde dehydrogenase gene families. Serum retinol binding-protein delivers all-trans-retinol (vitamin A) from blood to cells through two membrane receptors, Stra6 and Rbpr2. Stra6 and Rbpr2 convey retinol to cellular retinol binding-protein type 1 (Crbp1). Holo-Crbp1 delivers retinol to lecithin: retinol acyl transferase (Lrat) for esterification and storage. Lrat channels retinol directly into its active site from holo-Crbp1 by protein-protein interaction. The ratio apo-Crbp1/holo-Crbp1 directs flux of retinol into and out of retinyl esters, through regulating esterification vs ester hydrolysis. Multiple retinol dehydrogenases (Rdh1, Rdh10, Dhrs9, Rdhe2, Rdhe2s) channel retinol from holo-Crbp1 to generate retinal for ATRA biosynthesis. β-Carotene oxidase type 1 generates retinal from carotenoids, delivered by the scavenger receptor-B1. Retinal reductases (Dhrs3, Dhrs4, Rdh11) reduce retinal into retinol, thereby restraining ATRA biosynthesis. Retinal dehydrogenases (Raldh1, 2, 3) dehydrogenate retinal irreversibly into ATRA. ATRA regulates its own concentrations by inducing Lrat and ATRA degradative enzymes. ATRA exhibits hormesis. Its effects relate to its concentration as an inverted J-shaped curve, transitioning from beneficial in the "goldilocks" zone to toxicity, as concentrations increase. Hormesis has distorted understanding physiological effects of ATRA post-nataly using chow-diet fed, ATRA-dosed animal models. Cancer, immune deficiency and metabolic abnormalities result from mutations and/or insufficiency in Crbp1 and retinoid metabolizing enzymes.
Topics: Animals; Retinol-Binding Proteins; Retinol-Binding Proteins, Cellular; Tretinoin; Vitamin A
PubMed: 32359649
DOI: 10.1016/bs.mie.2020.02.003 -
Nutrients Aug 2018Vitamin A (all--retinol) is a fat-soluble micronutrient which together with its natural derivatives and synthetic analogues constitutes the group of retinoids. They are... (Review)
Review
Vitamin A (all--retinol) is a fat-soluble micronutrient which together with its natural derivatives and synthetic analogues constitutes the group of retinoids. They are involved in a wide range of physiological processes such as embryonic development, vision, immunity and cellular differentiation and proliferation. Retinoic acid (RA) is the main active form of vitamin A and multiple genes respond to RA signalling through transcriptional and non-transcriptional mechanisms. Vitamin A deficiency (VAD) is a remarkable public health problem. An adequate vitamin A intake is required in early lung development, alveolar formation, tissue maintenance and regeneration. In fact, chronic VAD has been associated with histopathological changes in the pulmonary epithelial lining that disrupt the normal lung physiology predisposing to severe tissue dysfunction and respiratory diseases. In addition, there are important alterations of the structure and composition of extracellular matrix with thickening of the alveolar basement membrane and ectopic deposition of collagen I. In this review, we show our recent findings on the modification of cell-junction proteins in VAD lungs, summarize up-to-date information related to the effects of chronic VAD in the impairment of lung physiology and pulmonary disease which represent a major global health problem and provide an overview of possible pathways involved.
Topics: Airway Remodeling; Animals; Epithelial-Mesenchymal Transition; Extracellular Matrix; Humans; Lung; Lung Diseases; Risk Factors; Signal Transduction; Vitamin A; Vitamin A Deficiency
PubMed: 30134568
DOI: 10.3390/nu10091132 -
Investigative Ophthalmology & Visual... Jan 2017Two-photon excited fluorescence (TPEF) imaging has potential as a functional tool for tracking visual pigment regeneration in the living eye. Previous studies have shown...
PURPOSE
Two-photon excited fluorescence (TPEF) imaging has potential as a functional tool for tracking visual pigment regeneration in the living eye. Previous studies have shown that all-trans-retinol is likely the chief source of time-varying TPEF from photoreceptors. Endogenous TPEF from retinol could provide the specificity desired for tracking the visual cycle. However, in vivo characterization of native retinol kinetics is complicated by visual stimulation from the imaging beam. We have developed an imaging scheme for overcoming these challenges and monitored the formation and clearance of retinol.
METHODS
Three macaques were imaged by using an in vivo two-photon ophthalmoscope. Endogenous TPEF was excited at 730 nm and recorded through the eye's pupil for more than 90 seconds. Two-photon excited fluorescence increased with onset of light and plateaued within 40 seconds, at which point, brief incremental stimuli were delivered at 561 nm. The responses of rods to stimulation were analyzed by using first-order kinetics.
RESULTS
Two-photon excited fluorescence resulting from retinol production corresponded to the fraction of rhodopsin bleached. The photosensitivity of rhodopsin was estimated to be 6.88 ± 5.50 log scotopic troland. The rate of retinol clearance depended on intensity of incremental stimulation. Clearance was faster for stronger stimuli and time constants ranged from 50 to 300 seconds.
CONCLUSIONS
This study demonstrates a method for rapidly measuring the rate of clearance of retinol in vivo. Moreover, TPEF generated due to retinol can be used as a measure of rhodopsin depletion, similar to densitometry. This enhances the utility of two-photon ophthalmoscopy as a technique for evaluating the visual cycle in the living eye.
Topics: Animals; Dark Adaptation; Female; Macaca fascicularis; Male; Models, Animal; Ophthalmoscopy; Optical Imaging; Retinal Pigments; Retinal Rod Photoreceptor Cells; Retinol-Binding Proteins; Rhodopsin; Vitamin A
PubMed: 28129424
DOI: 10.1167/iovs.16-20061 -
Nutrients Oct 2022All-trans-retinoic acid (RA), a metabolite of vitamin A (retinol), exerts profuse actions that enable multiple aspects of reproduction, embryonic development and...
All-trans-retinoic acid (RA), a metabolite of vitamin A (retinol), exerts profuse actions that enable multiple aspects of reproduction, embryonic development and post-natal regulation of energy metabolism, glucoregulatory control, organ function, and of the skeletal, immune, nervous and cardiovascular systems, as well as cell proliferation vs [...].
Topics: Pregnancy; Female; Humans; Tretinoin; Vitamin A; Autacoids
PubMed: 36364786
DOI: 10.3390/nu14214526 -
Nutrients Mar 2022Vitamin A (VA), all-trans-retinol (ROL), and its analogs are collectively called retinoids. Acting through the retinoic acid receptors RARα, RARβ, and RARγ,... (Review)
Review
Vitamin A (VA), all-trans-retinol (ROL), and its analogs are collectively called retinoids. Acting through the retinoic acid receptors RARα, RARβ, and RARγ, all-trans-retinoic acid, an active metabolite of VA, is a potent regulator of numerous biological pathways, including embryonic and somatic cellular differentiation, immune functions, and energy metabolism. The liver is the primary organ for retinoid storage and metabolism in humans. For reasons that remain incompletely understood, a body of evidence shows that reductions in liver retinoids, aberrant retinoid metabolism, and reductions in RAR signaling are implicated in numerous diseases of the liver, including hepatocellular carcinoma, non-alcohol-associated fatty liver diseases, and alcohol-associated liver diseases. Conversely, restoration of retinoid signaling, pharmacological treatments with natural and synthetic retinoids, and newer agonists for specific RARs show promising benefits for treatment of a number of these liver diseases. Here we provide a comprehensive review of the literature demonstrating a role for retinoids in limiting the pathogenesis of these diseases and in the treatment of liver diseases.
Topics: Humans; Liver Diseases; Receptors, Retinoic Acid; Retinoids; Tretinoin; Vitamin A
PubMed: 35406069
DOI: 10.3390/nu14071456