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1.
Immunity ; 54(11): 2447-2449, 2021 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-34758336

RESUMO

Retinol is shuttled to myeloid cells for conversion to retinoic acid, but the receptor facilitating uptake of SAA:retinol complexes on myeloid cells is unknown. In a recent issue of Science, Bang et al. (2021) use genetic and biochemical approaches to reveal this critical receptor to be LRP1 and show that this axis is essential for intestinal innate and adaptive immune responses.


Assuntos
Tretinoína , Vitamina A , Proteínas de Transporte , Tretinoína/metabolismo , Vitamina A/metabolismo
2.
FASEB J ; 35(11): e21934, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34599778

RESUMO

Dysfunction of the ATPase-binding Cassette Transporter protein (ABCA4) can lead to early onset macular degeneration, in particular to Stargardt disease. To enable translational research into this form of blindness, we evaluated the effect of Cas9-induced disruptions of the ABCA4 gene to potentially generate new transgenic rat models of the disease. We show that deletion of the short exon preceding the second nucleotide-binding domain is sufficient to drastically knock down protein levels and results in accumulation of retinoid dimers similar to that associated with Stargardt disease. Overexpression of the retinol dehydrogenase enzymes RDH8 and RDH12 can to a limited extent offset the increase in the bisretinoid levels in the Abca4Ex42-/ - KO rats possibly by restricting the time window in which retinal can dimerize before being reduced to retinol. However, in vivo imaging shows that overexpression of RDH8 can induce retinal degeneration. This may be due to the depletion in the outer segment of the cofactor NADPH, needed for RDH function. The translational potential of RDH therapy as well as other Stargardt disease therapies can be tested using the Abca4 knockdown rat model.


Assuntos
Oxirredutases do Álcool/genética , Oxirredutases do Álcool/metabolismo , Técnicas de Transferência de Genes , Doença de Stargardt/enzimologia , Doença de Stargardt/genética , Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/metabolismo , Animais , Modelos Animais de Doenças , Técnicas de Silenciamento de Genes , NADP/metabolismo , Células Fotorreceptoras/metabolismo , Ratos , Ratos Transgênicos , Vitamina A/metabolismo
4.
Nat Commun ; 12(1): 4975, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34404791

RESUMO

Plant cell wall hydrolysates contain not only sugars but also substantial amounts of acetate, a fermentation inhibitor that hinders bioconversion of lignocellulose. Despite the toxic and non-consumable nature of acetate during glucose metabolism, we demonstrate that acetate can be rapidly co-consumed with xylose by engineered Saccharomyces cerevisiae. The co-consumption leads to a metabolic re-configuration that boosts the synthesis of acetyl-CoA derived bioproducts, including triacetic acid lactone (TAL) and vitamin A, in engineered strains. Notably, by co-feeding xylose and acetate, an enginered strain produces 23.91 g/L TAL with a productivity of 0.29 g/L/h in bioreactor fermentation. This strain also completely converts a hemicellulose hydrolysate of switchgrass into 3.55 g/L TAL. These findings establish a versatile strategy that not only transforms an inhibitor into a valuable substrate but also expands the capacity of acetyl-CoA supply in S. cerevisiae for efficient bioconversion of cellulosic biomass.


Assuntos
Parede Celular/metabolismo , Engenharia Metabólica , Polissacarídeos/metabolismo , Saccharomyces cerevisiae/metabolismo , Acetilcoenzima A/metabolismo , Biomassa , Reatores Biológicos , Fermentação , Lignina , Pironas/metabolismo , Saccharomyces cerevisiae/genética , Vitamina A/metabolismo , Xilose/metabolismo
5.
Cell Signal ; 87: 110121, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34438017

RESUMO

The SARS-CoV-2 virus has caused a worldwide COVID-19 pandemic. In less than a year and a half, more than 200 million people have been infected and more than four million have died. Despite some improvement in the treatment strategies, no definitive treatment protocol has been developed. The pathogenesis of the disease has not been clearly elucidated yet. A clear understanding of its pathogenesis will help develop effective vaccines and drugs. The immunopathogenesis of COVID-19 is characteristic with acute respiratory distress syndrome and multiorgan involvement with impaired Type I interferon response and hyperinflammation. The destructive systemic effects of COVID-19 cannot be explained simply by the viral tropism through the ACE2 and TMPRSS2 receptors. In addition, the recently identified mutations cannot fully explain the defect in all cases of Type I interferon synthesis. We hypothesize that retinol depletion and resulting impaired retinoid signaling play a central role in the COVID-19 pathogenesis that is characteristic for dysregulated immune system, defect in Type I interferon synthesis, severe inflammatory process, and destructive systemic multiorgan involvement. Viral RNA recognition mechanism through RIG-I receptors can quickly consume a large amount of the body's retinoid reserve, which causes the retinol levels to fall below the normal serum levels. This causes retinoid insufficiency and impaired retinoid signaling, which leads to interruption in Type I interferon synthesis and an excessive inflammation. Therefore, reconstitution of the retinoid signaling may prove to be a valid strategy for management of COVID-19 as well for some other chronic, degenerative, inflammatory, and autoimmune diseases.


Assuntos
COVID-19/patologia , Transdução de Sinais/fisiologia , Vitamina A/metabolismo , COVID-19/imunologia , COVID-19/metabolismo , COVID-19/virologia , Sistema Nervoso Central/metabolismo , Proteína DEAD-box 58/metabolismo , Humanos , Tolerância Imunológica , Interferon Tipo I/metabolismo , Receptores Imunológicos/metabolismo , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Tropismo Viral/fisiologia , Vitamina A/sangue
6.
Biomolecules ; 11(8)2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34439893

RESUMO

Smith-Lemli-Opitz syndrome (SLOS) is a severe monogenic disorder resulting in low cholesterol and high 7-dehydrocholesterol (7-DHC) levels. 7-DHC-derived oxysterols likely contribute to disease pathophysiology, and thus antioxidant treatment might be beneficial because of high oxidative stress. In a three-year prospective study, we investigated the effects of vitamin E supplementation in six SLOS patients already receiving dietary cholesterol treatment. Plasma vitamin A and E concentrations were determined by the high-performance liquid chromatography (HPLC) method. At baseline, plasma 7-DHC, 8-dehydrocholesterol (8-DHC) and cholesterol levels were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The clinical effect of the supplementation was assessed by performing structured parental interviews. At baseline, patients were characterized by low or low-normal plasma vitamin E concentrations (7.19-15.68 µmol/L), while vitamin A concentrations were found to be normal or high (1.26-2.68 µmol/L). Vitamin E supplementation resulted in correction or significant elevation of plasma vitamin E concentration in all patients. We observed reduced aggression, self-injury, irritability, hyperactivity, attention deficit, repetitive behavior, sleep disturbance, skin photosensitivity and/or eczema in 3/6 patients, with notable individual variability. Clinical response to therapy was associated with a low baseline 7-DHC + 8-DHC/cholesterol ratio (0.2-0.4). We suggest that determination of vitamin E status is important in SLOS patients. Supplementation of vitamin E should be considered and might be beneficial.


Assuntos
Suplementos Nutricionais , Síndrome de Smith-Lemli-Opitz/sangue , Síndrome de Smith-Lemli-Opitz/terapia , Vitamina E/uso terapêutico , Adolescente , Alelos , Antioxidantes/metabolismo , Comportamento , Criança , Pré-Escolar , Colesterol na Dieta/metabolismo , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Desidrocolesteróis/sangue , Feminino , Humanos , Lipídeos/química , Masculino , Estresse Oxidativo , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/genética , Oxisteróis/metabolismo , Estudos Prospectivos , Esteróis/química , Espectrometria de Massas em Tandem , Vitamina A/metabolismo , Vitamina E/metabolismo , Adulto Jovem
7.
Cells ; 10(8)2021 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-34440929

RESUMO

The pandemics of obesity and type 2 diabetes have become a concern of public health. Nutrition plays a key role in these concerns. Insulin as an anabolic hormonal was discovered exactly 100 years ago due to its activity in controlling blood glucose level. Vitamin A (VA), a lipophilic micronutrient, has been shown to regulate glucose and fat metabolism. VA's physiological roles are mainly mediated by its metabolite, retinoic acid (RA), which activates retinoic acid receptors (RARs) and retinoid X receptors (RXRs), which are two transcription factors. The VA status and activations of RARs and RXRs by RA and synthetic agonists have shown to affect the glucose and lipid metabolism in animal models. Both insulin and RA signaling systems regulate the expression levels of genes involved in the regulation of hepatic glucose and lipid metabolism. Interactions of insulin and RA signaling systems have been observed. This review is aimed at summarizing the history of diabetes, insulin and VA signaling systems; the effects of VA status and activation of RARs and RXRs on metabolism and RAR and RXR phosphorylation; and possible interactions of insulin and RA in the regulation of hepatic genes for glucose and lipid metabolism. In addition, some future research perspectives for understanding of nutrient and hormone interactions are provided.


Assuntos
Glucose/metabolismo , Insulina/metabolismo , Metabolismo dos Lipídeos/fisiologia , Fígado/metabolismo , Vitamina A/metabolismo , Animais , Humanos , Receptores do Ácido Retinoico/metabolismo , Receptores X de Retinoides/metabolismo , Transdução de Sinais/fisiologia
8.
J Biol Chem ; 297(3): 101074, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34391781

RESUMO

Impaired dark adaptation (DA), a defect in the ability to adjust to dimly lit settings, is a universal hallmark of aging. However, the mechanisms responsible for impaired DA are poorly understood. Vitamin A byproducts, such as vitamin A dimers, are small molecules that form in the retina during the vitamin A cycle. We show that later in life, in the human eye, these byproducts reach levels commensurate with those of vitamin A. In mice, selectively inhibiting the formation of these byproducts, with the investigational drug C20D3-vitamin A, results in faster DA. In contrast, acutely increasing these ocular byproducts through exogenous delivery leads to slower DA, with otherwise preserved retinal function and morphology. Our findings reveal that vitamin A cycle byproducts alone are sufficient to cause delays in DA and suggest that they may contribute to universal age-related DA impairment. Our data further indicate that the age-related decline in DA may be tractable to pharmacological intervention by C20D3-vitamin A.


Assuntos
Adaptação à Escuridão/fisiologia , Retina/metabolismo , Vitamina A/metabolismo , Envelhecimento , Animais , Adaptação à Escuridão/genética , Olho/efeitos dos fármacos , Olho/metabolismo , Humanos , Degeneração Macular/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Retina/efeitos dos fármacos , Degeneração Retiniana/fisiopatologia , Epitélio Pigmentado da Retina/efeitos dos fármacos , Epitélio Pigmentado da Retina/metabolismo , Acuidade Visual/efeitos dos fármacos , Acuidade Visual/fisiologia , Vitamina A/antagonistas & inibidores , Vitamina A/fisiologia
9.
Nutrients ; 13(6)2021 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-34204998

RESUMO

The association between obesity and vitamin A has been studied. Some studies point to the anti-obesity activity related to this vitamin, carotenoids with provitamin A activity, and carotenoid conversion products. This performance has been evaluated in respect of adipogenesis, metabolic activity, oxidation processes, secretory function, and oxidative stress modulation, showing a new property attributed to vitamin A in preventing and treating obesity. However, vitamin A and its precursors are highly sensitive and easily degraded when subjected to heat, the presence of light, and oxygen, in addition to losses related to the processes of digestion and absorption. In this context, encapsulation presents itself as an alternative capable of increasing vitamin A's stability in the face of unfavorable conditions in the environment, which can reduce its functionality. Considering that vitamin A's status shows a strong correlation with obesity and is an innovative theme, this article addresses the associations between vitamin A's consumption and its precursors, encapsulated or not, and its physiological effects on obesity. The present narrative review points out those recent studies that demonstrate that vitamin A and its encapsulated precursors have the most preserved functionality, which guarantees better effects on obesity therapy.


Assuntos
Obesidade/tratamento farmacológico , Vitamina A/uso terapêutico , Vitaminas/uso terapêutico , Carotenoides/metabolismo , Sistemas de Liberação de Medicamentos , Humanos , Obesidade/prevenção & controle , Vitamina A/administração & dosagem , Vitamina A/metabolismo , Vitaminas/administração & dosagem , Vitaminas/metabolismo
10.
Cell Mol Life Sci ; 78(17-18): 6105-6117, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34297165

RESUMO

Transthyretin (TTR) is an extracellular protein mainly produced in the liver and choroid plexus, with a well-stablished role in the transport of thyroxin and retinol throughout the body and brain. TTR is prone to aggregation, as both wild-type and mutated forms of the protein can lead to the accumulation of amyloid deposits, resulting in a disease called TTR amyloidosis. Recently, novel activities for TTR in cell biology have emerged, ranging from neuronal health preservation in both central and peripheral nervous systems, to cellular fate determination, regulation of proliferation and metabolism. Here, we review the novel literature regarding TTR new cellular effects. We pinpoint TTR as major player on brain health and nerve biology, activities that might impact on nervous systems pathologies, and assign a new link between TTR and angiogenesis and cancer. We also explore the molecular mechanisms underlying TTR activities at the cellular level, and suggest that these might go beyond its most acknowledged carrier functions and include interaction with receptors and activation of intracellular signaling pathways.


Assuntos
Amiloidose/etiologia , Pré-Albumina/metabolismo , Amiloidose/metabolismo , Sistema Nervoso Central/metabolismo , Humanos , Neurônios/citologia , Neurônios/metabolismo , Pré-Albumina/química , Pré-Albumina/genética , Agregados Proteicos/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Tiroxina/química , Tiroxina/metabolismo , Vitamina A/química , Vitamina A/metabolismo
11.
Front Immunol ; 12: 671283, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34305901

RESUMO

The vitamin A derivative, retinoid acid (RA) is key player in guiding adaptive mucosal immune responses. However, data on the uptake and metabolism of vitamin A within human immune cells has remained largely elusive because retinoids are small, lipophilic molecules which are difficult to detect. To overcome this problem and to be able to study the effect of vitamin A metabolism in human immune cell subsets, we have synthesized novel bio-orthogonal retinoid-based probes (clickable probes), which are structurally and functionally indistinguishable from vitamin A. The probes contain a functional group (an alkyne) to conjugate to a fluorogenic dye to monitor retinoid molecules in real-time in immune cells. We demonstrate, by using flow cytometry and microscopy, that multiple immune cells have the capacity to internalize retinoids to varying degrees, including human monocyte-derived dendritic cells (DCs) and naïve B lymphocytes. We observed that naïve B cells lack the enzymatic machinery to produce RA, but use exogenous retinoic acid to enhance CD38 expression. Furthermore, we showed that human DCs metabolize retinal into retinoic acid, which in co-culture with naïve B cells led to of the induction of CD38 expression. These data demonstrate that in humans, DCs can serve as an exogenous source of RA for naïve B cells. Taken together, through the use of clickable vitamins our data provide valuable insight in the mechanism of vitamin A metabolism and its importance for human adaptive immunity.


Assuntos
Linfócitos B/imunologia , Química Click/métodos , Células Dendríticas/imunologia , Vitamina A/metabolismo , ADP-Ribosil Ciclase 1/metabolismo , Imunidade Adaptativa , Células Cultivadas , Técnicas de Cocultura , Cobre/metabolismo , Citometria de Fluxo , Corantes Fluorescentes , Humanos , Tretinoína/química , Tretinoína/metabolismo , Regulação para Cima , Vitamina A/química
12.
Sci Rep ; 11(1): 12642, 2021 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-34135397

RESUMO

Malnutrition affects growth and development in humans and causes socio-economic losses. Normal maize is deficient in essential amino acids, lysine and tryptophan; and vitamin-A. Crop biofortification is a sustainable and economical approach to alleviate micronutrient malnutrition. We combined favorable alleles of crtRB1 and lcyE genes into opaque2 (o2)-based four inbreds viz. QLM11, QLM12, QLM13, and QLM14 using marker-assisted backcross breeding. These are parents of quality protein maize versions of two elite hybrids viz. Buland and PMH1, grown in India. Gene-based SSRs for o2 and InDel markers for crtRB1 and lcyE were successfully employed for foreground selection in BC1F1, BC2F1, and BC2F2 generations. The recurrent parent genome recovery ranged from 88.9 to 96.0% among introgressed progenies. Kernels of pyramided lines possessed a high concentration of proA (7.14-9.63 ppm), compared to 1.05 to 1.41 ppm in the recurrent parents, while lysine and tryptophan ranged from 0.28-0.44% and 0.07-0.09%, respectively. The reconstituted hybrids (RBuland and RPMH1) showed significant enhancement of endosperm proA (6.97-9.82 ppm), tryptophan (0.07-0.09%), and lysine (0.29-0.43%), while grain yield was at par with their original versions. The dissemination of reconstituted hybrids holds significant promise to alleviate vitamin-A deficiency and protein-energy malnutrition in developing countries.


Assuntos
Biofortificação/métodos , Zea mays/genética , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Grão Comestível/genética , Grão Comestível/metabolismo , Endosperma/metabolismo , Genes de Plantas , Marcadores Genéticos , Humanos , Liases Intramoleculares/genética , Liases Intramoleculares/metabolismo , Lisina/metabolismo , Melhoramento Vegetal/métodos , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Triptofano/metabolismo , Vitamina A/metabolismo , Deficiência de Vitamina A/prevenção & controle , beta Caroteno/metabolismo
13.
Food Chem ; 359: 129911, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33951608

RESUMO

We showed that black soldier fly larvae reared on fruits and vegetables rich in provitamin A carotenoids can accumulate significant amounts of these vitamin A precursors. Using a simulated gastro-intestinal digestion model, we demonstrated that α- and ß-carotene from the larvae are as bioaccessible as from the fruits and vegetables they were reared on. We calculated that provitamin A carotenoid-rich larvae have the capacity to provide more vitamin A than fruits and vegetables rich in these molecules. Remarkably, the incorporation of usual quantities of these larvae in feed could cover the needs of several production animals for this vitamin. Thus, our findings suggest that rearing black soldier fly larvae on by-products or waste rich in provitamin A carotenoids could be a sustainable strategy to recycle a fraction of vitamin A back into the food chain and could represent a new approach to fight against vitamin A deficiency.


Assuntos
Carotenoides/metabolismo , Dípteros , Frutas , Provitaminas/metabolismo , Verduras , Vitamina A/metabolismo , Animais , Dieta , Frutas/metabolismo , Larva/metabolismo , Verduras/metabolismo , beta Caroteno/metabolismo
14.
Front Immunol ; 12: 670632, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33995407

RESUMO

Innate lymphoid cells (ILCs) are a group of innate immune cells that possess overlapping features with T cells, although they lack antigen-specific receptors. ILCs consist of five subsets-ILC1, ILC2, ILC3, lymphoid tissue inducer (LTi-like) cells, and natural killer (NK) cells. They have significant functions in mediating various immune responses, protecting mucosal barrier integrity and maintaining tissue homeostasis in the lung, skin, intestines, and liver. ILCs react immediately to signals from internal and external sources. Emerging evidence has revealed that dietary micronutrients, such as various vitamins and minerals can significantly modulate immune responses through ILCs and subsequently affect human health. It has been demonstrated that micronutrients control the development and proliferation of different types of ILCs. They are also potent immunoregulators in several autoimmune diseases and play vital roles in resolving local inflammation. Here, we summarize the interplay between several essential micronutrients and ILCs to maintain epithelial barrier functions in various mucosal tissues and discuss their limitations and potentials for promoting human health.


Assuntos
Dieta/métodos , Linfócitos/imunologia , Micronutrientes/metabolismo , Animais , Translocador Nuclear Receptor Aril Hidrocarboneto/metabolismo , Homeostase , Humanos , Imunidade Inata , Vitamina A/metabolismo , Vitamina D/metabolismo
15.
Molecules ; 26(6)2021 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-33801011

RESUMO

Vitamin A is a fat-soluble micronutrient essential for growth, immunity, and good vision. The preformed retinol is commonly found in food of animal origin whereas provitamin A is derived from food of plant origin. This review summarises the current evidence from animal, human and cell-culture studies on the effects of vitamin A towards bone health. Animal studies showed that the negative effects of retinol on the skeleton were observed at higher concentrations, especially on the cortical bone. In humans, the direct relationship between vitamin A and poor bone health was more pronounced in individuals with obesity or vitamin D deficiency. Mechanistically, vitamin A differentially influenced the stages of osteogenesis by enhancing early osteoblastic differentiation and inhibiting bone mineralisation via retinoic acid receptor (RAR) signalling and modulation of osteocyte/osteoblast-related bone peptides. However, adequate vitamin A intake through food or supplements was shown to maintain healthy bones. Meanwhile, provitamin A (carotene and ß-cryptoxanthin) may also protect bone. In vitro evidence showed that carotene and ß-cryptoxanthin may serve as precursors for retinoids, specifically all-trans-retinoic acid, which serve as ligand for RARs to promote osteogenesis and suppressed nuclear factor-kappa B activation to inhibit the differentiation and maturation of osteoclasts. In conclusion, we suggest that both vitamin A and provitamin A may be potential bone-protecting agents, and more studies are warranted to support this hypothesis.


Assuntos
Osso e Ossos/metabolismo , Obesidade/metabolismo , Osteogênese , Receptores do Ácido Retinoico , Vitamina A/metabolismo , Deficiência de Vitamina D/metabolismo , Animais , Humanos
16.
Int J Mol Sci ; 22(7)2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33805295

RESUMO

Bladder cancer (BC) is the tenth most common cancer worldwide with a high recurrence rate, morbidity and mortality. Therefore, chemoprevention and improved treatment of BC are of paramount importance. Epidemiological studies suggest that adequate vitamin A intake may be associated with reduced BC risk. In addition, retinoids, natural and synthetic derivatives of vitamin A, are intensively studied in cancer research due to their antioxidant properties and their ability to regulate cell growth, differentiation, and apoptosis. Findings from in vivo and in vitro models of BC show great potential for the use of retinoids in the chemoprevention and treatment of BC. However, translation to the clinical practice is limited. In this narrative review we discuss: (i) vitamin A and retinoid metabolism and retinoic acid signalling, (ii) the pathobiology of BC and the need for chemoprevention, (iii) the epidemiological evidence for the role of dietary vitamin A in BC, (iv) mechanistic insights obtained from in vivo and in vitro models, (v) clinical trials of retinoids and the limitations of retinoid use, (vi) novel systems of retinoid delivery, and (vii) components of retinoid signalling pathways as potential novel therapeutic targets.


Assuntos
Anticarcinógenos/uso terapêutico , Antineoplásicos/uso terapêutico , Retinoides/metabolismo , Neoplasias da Bexiga Urinária/tratamento farmacológico , Vitamina A/metabolismo , Animais , Apoptose , Diferenciação Celular , Humanos , Retinoides/farmacologia , Retinoides/uso terapêutico , Transdução de Sinais , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/fisiopatologia , Neoplasias da Bexiga Urinária/prevenção & controle , Vitamina A/farmacologia , Vitamina A/uso terapêutico
17.
Nutrients ; 13(3)2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33809241

RESUMO

Vitamin A is a family of derivatives synthesized from carotenoids acquired from the diet and can be converted in animals to bioactive forms essential for life. Vitamin A1 (all-trans-retinol/ATROL) and provitamin A1 (all-trans-ß,ß-carotene/ATBC) are precursors of all-trans-retinoic acid acting as a ligand for the retinoic acid receptors. The contribution of ATROL and ATBC to formation of 9-cis-13,14-dihydroretinoic acid (9CDHRA), the only endogenous retinoid acting as retinoid X receptor (RXR) ligand, remains unknown. To address this point novel and already known retinoids and carotenoids were stereoselectively synthesized and administered in vitro to oligodendrocyte cell culture and supplemented in vivo (orally) to mice with a following high-performance liquid chromatography-mass spectrometry (HPLC-MS)/UV-Vis based metabolic profiling. In this study, we show that ATROL and ATBC are at best only weak and non-selective precursors of 9CDHRA. Instead, we identify 9-cis-13,14-dihydroretinol (9CDHROL) and 9-cis-13,14-dihydro-ß,ß-carotene (9CDHBC) as novel direct nutritional precursors of 9CDHRA, which are present endogenously in humans and the human food chain matrix. Furthermore, 9CDHROL displayed RXR-dependent promnemonic activity in working memory test similar to that reported for 9CDHRA. We also propose that the endogenous carotenoid 9-cis-ß,ß-carotene (9CBC) can act as weak, indirect precursor of 9CDHRA via hydrogenation to 9CDHBC and further metabolism to 9CDHROL and/or 9CDHRA. In summary, since classical vitamin A1 is not an efficient 9CDHRA precursor, we conclude that this group of molecules constitutes a new class of vitamin or a new independent member of the vitamin A family, named "Vitamin A5/X".


Assuntos
Receptores X de Retinoides/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Tretinoína/análogos & derivados , Vitaminas/farmacologia , Animais , Células Cultivadas , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Masculino , Memória de Curto Prazo/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Oligodendroglia/efeitos dos fármacos , Provitaminas/análise , Provitaminas/síntese química , Provitaminas/farmacologia , Tretinoína/farmacologia , Vitamina A/análogos & derivados , Vitamina A/metabolismo , Vitaminas/análise , Vitaminas/síntese química
18.
J Sci Food Agric ; 101(14): 6027-6035, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33852732

RESUMO

BACKGROUND: Newly developed yellow biofortified cassava has been adjudged as a cost-effective solution to vitamin A deficiency in low- and middle-income countries with high cassava intake such as Nigeria. In this study, yellow cassava was developed into a novel pasta enriched with amaranth vegetable and tested among consumers. Attitudes, perception, motives for consumption and perceived barriers were ascertained using focus group discussions and randomised face-to-face interviews, while liking, preference and ranking of the novel food were established through consumer sensory perception. RESULTS: Willingness to consume the new food, low food neophobia (32%), a health-driven consumption pattern, as well as an appreciable acceptance for the developed pasta, was established among the consumers. Ugwu (Telfairia occidentalis) was found to be the most preferred leafy vegetable. The yellow cassava pasta was ranked better than the conventional white cassava. CONCLUSION: This study shows new avenues to valorise yellow cassava by which nutrition security can be improved in low- and middle-income countries of Africa. © 2021 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.


Assuntos
Comportamento do Consumidor , Alimentos Fortificados/análise , Manihot/metabolismo , Verduras/metabolismo , Adolescente , Adulto , Idoso , Biofortificação , Feminino , Humanos , Masculino , Manihot/química , Pessoa de Meia-Idade , Nigéria , Estado Nutricional , Folhas de Planta/química , Folhas de Planta/metabolismo , Paladar , Verduras/química , Vitamina A/análise , Vitamina A/metabolismo , Adulto Jovem
19.
Am J Clin Nutr ; 113(5): 1372-1380, 2021 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-33675342

RESUMO

BACKGROUND: Lactating women are at increased risk for vitamin A (VA) deficiency due to demands for breast milk content and limited hepatic stores for women in some countries. Previously, consumption of triple-fortified rice, which included VA, iron, and zinc, successfully improved the VA status of Thai children in whom their total body VA stores (TBSs) were doubled in 2 mo. OBJECTIVE: This study assessed the efficacy of consuming VA-fortified rice, which delivered 500 µg retinol activity equivalents (RAEs)/d, on TBSs and estimated total liver VA reserves (TLRs) in Thai lactating women using the retinol isotope dilution (RID) test. METHODS: A randomized controlled trial was conducted with 70 lactating women (n = 35/group) who received either VA-fortified rice (500 µg RAEs/d) or unfortified rice for 14 wk on weekdays only. Serum retinol concentrations (SRs), C-reactive protein, and TBSs were assessed before and after the intervention. The paired 13C-RID test was used to measure TBSs. After a baseline blood sample, 2.0 µmol [14,15]-13C2-retinyl acetate was administered orally. A follow-up blood sample was drawn 14 d later. The RID test was repeated after the intervention. RESULTS: TBSs increased significantly (P < 0.05) in the intervention group from 240 (182, 316) to 331 (251, 447) [geometric means (95% CIs)] µmol retinol, and this change in TBSs was significantly higher (P < 0.05) than that in the control group [+52.9 (-74, 453) compared with -4.3 (-106, 275) µmol retinol]. Estimated TLRs indicated a high prevalence of VA deficiency among these lactating women. Initial and final SRs did not differ by group and did not change over the course of the intervention. CONCLUSION: VA-fortified rice improved the VA status of lactating women by increasing TBSs. A targeted approach to disseminate VA interventions among vulnerable groups should be considered in some contexts. This trial was registered at clinicaltrials.gov as NCT03056625.


Assuntos
Alimentos Fortificados , Oryza/química , Oryza/genética , Vitamina A/genética , Vitamina A/metabolismo , Adulto , Método Duplo-Cego , Feminino , Humanos , Ferro , Lactação , Tailândia , Adulto Jovem , Zinco
20.
Am J Clin Nutr ; 113(5): 1209-1220, 2021 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-33693468

RESUMO

BACKGROUND: Replacement of conventional staples with biofortified or industrially fortified staples in household diets may increase maternal breast milk retinol content and vitamin A intakes from complementary foods, improving infant total body stores (TBS) of vitamin A. OBJECTIVES: To determine whether biofortified or industrially fortified maize consumption by Zambian women and their breastfeeding infants could improve milk retinol concentration and infant TBS. METHODS: We randomly assigned 255 lactating women and their 9-mo-old infants to a 90-d intervention providing 0 µg retinol equivalents (RE)/d as conventional maize or ∼315 µg RE/d to mothers and ∼55 µg RE/d to infants as provitamin A carotenoid-biofortified maize or retinyl palmitate-fortified maize. Outcomes were TBS, measured by retinol isotope dilution in infants (primary), and breast milk retinol, measured by HPLC in women (secondary). RESULTS: The intervention groups were comparable at baseline. Loss to follow-up was 10% (n = 230 mother-infant pairs). Women consumed 92% of the intended 287 g/d and infants consumed 82% of the intended 50 g/d maize. The baseline geometric mean (GM) milk retinol concentration was 1.57 µmol/L (95% CI: 1.45, 1.69 µmol/L), and 24% of women had milk retinol <1.05 µmol/L. While mean milk retinol did not change in the biofortified arm (ß: 0.11; 95% CI: -0.02, 0.24), the intervention reduced low milk retinol (RR: 0.42; 95% CI: 0.21, 0.85). Fortified maize increased mean milk retinol (ß: 0.17; 95% CI: 0.04, 0.30) and reduced the prevalence of low milk retinol (RR: 0.46; 95% CI: 0.25, 0.82). The baseline GM TBS was 178 µmol (95% CI: 166, 191 µmol). This increased by 24 µmol (± 136) over the 90-d intervention period, irrespective of treatment group. CONCLUSIONS: Both biofortified and fortified maize consumption improved milk retinol concentration. This did not translate into greater infant TBS, most likely due to adequate TBS at baseline. This trial was registered at clinicaltrials.gov as NCT02804490.


Assuntos
Biofortificação , Diterpenos/administração & dosagem , Leite Humano/química , Ésteres de Retinil/administração & dosagem , Vitamina A/administração & dosagem , Vitamina A/química , Zea mays/genética , Adulto , Aleitamento Materno , Estudos de Coortes , Feminino , Alimentos Fortificados , Humanos , Lactente , Vitamina A/metabolismo , Zâmbia
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