RESUMEN
BACKGROUND: This study aimed to investigate the impact of Vitamin A (VA) on intestinal glucose metabolic phenotypes. METHODS: Male C57BL/6 mice were randomized assigned to a VA-normal diet (VAN) or a VA-deficient diet (VAD) for 12 weeks. After12 weeks, the VAD mice were given 30 IU/g/d retinol for 10 days and VAN diet (VADN) for 10 weeks. By using glucose tolerance tests, immunofluorescence staining, quantitative polymerase chain reaction, siRNA transduction, and enzyme-linked immunosorbent assay, the glucose metabolic phenotypes as well as secretory function and intracellular hormone changes of STC-1 were assessed. RESULTS: VAD mice showed a decrease of glucose-stimulated insulin secretion and a loss of intestinal glucagon-like peptide-1 (GLP-1) expression. Through reintroducing dietary VA to VAD mice, the intestinal VA levels, GLP-1 expression and normal glucose can be restored. The incubation with retinol increased VA signaling factors expression within STC-1 cells, especially retinoic acid receptor ß (RARß). The activation of RARß restored intracellular incretin hormone synthesis and secretory function. CONCLUSIONS: VA deficiency leads to an imbalance of intestinal glucose metabolic phenotypes through a mechanism involving RARß signaling pathway, suggesting a new method to achieve the treatment for VAD induced glucose metabolism impairment.
Asunto(s)
Péptido 1 Similar al Glucagón , Incretinas , Ratones Endogámicos C57BL , Receptores de Ácido Retinoico , Vitamina A , Animales , Masculino , Vitamina A/metabolismo , Ratones , Receptores de Ácido Retinoico/metabolismo , Receptores de Ácido Retinoico/genética , Incretinas/metabolismo , Péptido 1 Similar al Glucagón/metabolismo , Deficiencia de Vitamina A/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Secreción de Insulina/efectos de los fármacos , Secreción de Insulina/fisiologíaRESUMEN
Vitamin A (VA) has many functions in the body, some of which are key for the development and functioning of the nervous system, while some others might indirectly influence neural function. Both hypovitaminosis and hypervitaminosis A can lead to clinical manifestations of concern for individuals and for general global health. Scientific evidence on the link between VA and autism spectrum disorder (ASD) is growing, with some clinical studies and accumulating results obtained from basic research using cellular and animal models. Remarkably, it has been shown that VA deficiency can exacerbate autistic symptomatology. In turn, VA supplementation has been shown to be able to improve autistic symptomatology in selected groups of individuals with ASD. However, it is important to recognize that ASD is a highly heterogeneous condition. Therefore, it is important to clarify how and when VA supplementation can be of benefit for affected individuals. Here we delve into the relationship between VA and ASD, discussing clinical observations and mechanistic insights obtained from research on selected autistic syndromes and laboratory models to advance in defining how the VA signaling pathway can be exploited for treatment of ASD.
Asunto(s)
Trastorno del Espectro Autista , Vitamina A , Trastorno del Espectro Autista/metabolismo , Humanos , Vitamina A/metabolismo , Animales , Deficiencia de Vitamina A/complicaciones , Deficiencia de Vitamina A/metabolismo , Suplementos DietéticosRESUMEN
The first evidence of the existence of vitamin A was the observation 1881 that a substance present in small amounts in milk was necessary for normal development and life. It was not until more than 100 years later that it was understood that vitamin A acts as a hormone through nuclear receptors. Unlike classical hormones, vitamin A cannot be synthesized by the body but needs to be supplied by the food as retinyl esters in animal products and ß-carotene in vegetables and fruits. Globally, vitamin A deficiency is a huge health problem, but in the industrialized world excess of vitamin A has been suggested to be a risk factor for secondary osteoporosis and enhanced susceptibility to fractures. Preclinical studies unequivocally have shown that increased amounts of vitamin A cause decreased cortical bone mass and weaker bones due to enhanced periosteal bone resorption. Initial clinical studies demonstrated a negative association between intake of vitamin A, as well as serum levels of vitamin A, and bone mass and fracture susceptibility. In some studies, these observations have been confirmed, but in other studies no such associations have been observed. One meta-analysis found that both low and high serum levels of vitamin A were associated with increased relative risk of hip fractures. Another meta-analysis also found that low levels of serum vitamin A increased the risk for hip fracture but could not find any association with high serum levels of vitamin A and hip fracture. It is apparent that more clinical studies, including large numbers of incident fractures, are needed to determine which levels of vitamin A that are harmful or beneficial for bone mass and fracture. It is the aim of the present review to describe how vitamin A was discovered and how vitamin A is absorbed, metabolized and is acting as a ligand for nuclear receptors. The effects by vitamin A in preclinical studies are summarized and the clinical investigations studying the effect by vitamin A on bone mass and fracture susceptibility are discussed in detail.
Asunto(s)
Densidad Ósea , Fracturas Óseas , Vitamina A , Humanos , Vitamina A/metabolismo , Vitamina A/sangre , Animales , Fracturas Óseas/metabolismo , Fracturas Óseas/etiología , Fracturas Óseas/epidemiología , Transducción de Señal , Osteoporosis/metabolismo , Deficiencia de Vitamina A/metabolismo , Deficiencia de Vitamina A/complicaciones , Huesos/metabolismoRESUMEN
Vitamin A deficiency (VAD) induced TGF-ß hyperactivation and reduced expression of cell adhesion proteins in the lung, suggesting that the disruption of retinoic acid (RA) signaling leads to epithelial-mesenchymal transition (EMT). To elucidate the role of lung vitamin A status in EMT, several EMT markers and the expression of the proprotein convertase furin, which activates TGF-ß, were analyzed in two experimental models. Our in vivo model included control rats, VAD rats, and both control rats and VAD rats, treated with RA. For the in vitro studies, human bronchoalveolar epithelial cells treated with RA were used. Our data show that EMT and furin are induced in VAD rats. Furthermore, furin expression continues to increase much more markedly after treatment of VAD rats with RA. In control rats and cell lines, an acute RA treatment induced a significant increase in furin expression, concomitant with changes in EMT markers. A ChIP assay demonstrated that RA directly regulates furin transcription. These results emphasize the importance of maintaining vitamin A levels within the physiological range since both levels below and above this range can cause adverse effects that, paradoxically, could be similar. The role of furin in EMT is discussed.
Asunto(s)
Transición Epitelial-Mesenquimal , Furina , Pulmón , Deficiencia de Vitamina A , Vitamina A , Furina/metabolismo , Transición Epitelial-Mesenquimal/efectos de los fármacos , Animales , Humanos , Pulmón/metabolismo , Pulmón/efectos de los fármacos , Vitamina A/farmacología , Vitamina A/metabolismo , Ratas , Deficiencia de Vitamina A/metabolismo , Masculino , Tretinoina/farmacología , Células Epiteliales/metabolismo , Células Epiteliales/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Factor de Crecimiento Transformador beta/metabolismo , Línea Celular , Ratas WistarRESUMEN
Vitamin A is an important nutrient for multiple physiological functions. To elucidate the role of vitamin A in vivo, vitamin A-deficient diets have been often used in mice to establish a vitamin A-deficiency model. However, the information on the appropriate feeding periods and time course of changes in vitamin A content in organs after the start of vitamin A-deficient diet feeding is lacking. This study aimed to assess the retinoids levels in liver and white adipose tissue in mice fed a vitamin A-deficient diet for ≤8 weeks. High-performance liquid chromatography was used to measure the retinoids levels in liver and white adipose tissue every 2 weeks for ≤8 weeks. Vitamin A-deficient diet feeding significantly decreased retinol in the liver over 6 weeks, but retinyl palmitate, a main storage form of vitamin A, was not changed over 8 weeks. The plasma retinol level remained constant throughout the experiment. In white adipose tissue, retinyl palmitate gradually decreased over 8 weeks. These results indicate that vitamin A-deficient diet feeding longer than 6 weeks reduced retinol in liver and retinyl palmitate in white adipose tissue over 8 weeks, although it is not enough for the induction of a whole-body vitamin A deficiency.
Asunto(s)
Tejido Adiposo Blanco , Dieta , Diterpenos , Hígado , Retinoides , Ésteres de Retinilo , Deficiencia de Vitamina A , Vitamina A , Animales , Hígado/metabolismo , Vitamina A/metabolismo , Deficiencia de Vitamina A/metabolismo , Ésteres de Retinilo/metabolismo , Retinoides/metabolismo , Diterpenos/metabolismo , Masculino , Tejido Adiposo Blanco/metabolismo , Factores de Tiempo , Ratones Endogámicos C57BL , Ratones , Tejido Adiposo/metabolismoRESUMEN
Vitamin A (VA) is critical for many biological processes, including embryonic development, hormone production and function, the maintenance and modulation of immunity, and the homeostasis of epithelium and mucosa. Specifically, VA affects cell integrity, cytokine production, innate immune cell activation, antigen presentation, and lymphocyte trafficking to mucosal surfaces. VA also has been reported to influence the gut microbiota composition and diversity. Consequently, VA deficiency (VAD) results in the imbalanced production of inflammatory and immunomodulatory cytokines, intestinal inflammation, weakened mucosal barrier functions, reduced reactive oxygen species (ROS) and disruption of the gut microbiome. Although VAD is primarily known to cause xerophthalmia, its role in the impairment of anti-infectious defense mechanisms is less defined. Infectious diseases lead to temporary anorexia and lower dietary intake; furthermore, they adversely affect VA status by interfering with VA absorption, utilization and excretion. Thus, there is a tri-directional relationship between VAD, immune response and infections, as VAD affects immune response and predisposes the host to infection, and infection decreases the intestinal absorption of the VA, thereby contributing to secondary VAD development. This has been demonstrated using nutritional and clinical studies, radiotracer studies and knockout animal models. An in-depth understanding of the relationship between VAD, immune response, gut microbiota and infections is critical for optimizing vaccine efficacy and the development of effective immunization programs for countries with high prevalence of VAD. Therefore, in this review, we have comprehensively summarized the existing knowledge regarding VAD impacts on immune responses to infections and post vaccination. We have detailed pathological conditions associated with clinical and subclinical VAD, gut microbiome adaptation to VAD and VAD effects on the immune responses to infection and vaccines.
Asunto(s)
Microbioma Gastrointestinal , Deficiencia de Vitamina A , Animales , Embarazo , Femenino , Deficiencia de Vitamina A/metabolismo , Vitamina A , Citocinas , Modelos AnimalesRESUMEN
Vitamin A (retinol) is an essential, fat-soluble vitamin that plays critical roles in embryonic development, vision, immunity, and reproduction. Severe vitamin A deficiency results in profound embryonic dysgenesis, blindness, and infertility. The roles of bioactive vitamin A metabolites in regulating cell proliferation, cellular differentiation, and immune cell function form the basis of their clinical use in the treatment of dermatologic conditions and hematologic malignancies. Increasingly, vitamin A also has been recognized to play important roles in cardiometabolic health, including the regulation of adipogenesis, energy partitioning, and lipoprotein metabolism. While these roles are strongly supported by animal and in vitro studies, they remain poorly understood in human physiology and disease. This review briefly introduces vitamin A biology and presents the key preclinical data that have generated interest in vitamin A as a mediator of cardiometabolic health. The review also summarizes clinical studies performed to date, highlighting the limitations of many of these studies and the ongoing controversies in the field. Finally, additional perspectives are suggested that may help position vitamin A metabolism within a broader biological context and thereby contribute to enhanced understanding of vitamin A's complex roles in clinical cardiometabolic disease.
Asunto(s)
Enfermedades Cardiovasculares , Deficiencia de Vitamina A , Adipogénesis , Animales , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/etiología , Femenino , Homeostasis/fisiología , Humanos , Embarazo , Vitamina A/metabolismo , Vitamina A/uso terapéutico , Deficiencia de Vitamina A/tratamiento farmacológico , Deficiencia de Vitamina A/metabolismoRESUMEN
Vitamin A plays a prominent role for maintaining optimal bone status, but its impact upon the bone in response to vitamin A deficiency is not well defined. The purpose of this study was to evaluate how replenishing vitamin A by either whole food cod liver oil (COD) or the active metabolite of vitamin A, retinoic acid (RA), altered bone thickness of vitamin A-deficient (VAD) rats. Weanling rats were administered a control diet (CTRL) or VAD diet for 9 weeks. This was followed by four weeks of treatment in which the VAD group was divided into the following 4 subgroups: (1) VAD (9 weeks)-VAD (4 weeks); (2) VAD-CTRL; (3) VAD-COD; and (4) VAD-RA. Compared to controls, VAD rats had thicker bones which showed marked dysplasia. VAD-rats treated with COD produced a thinner bone that was not significantly different from that of untreated rats. In contrast, RA did not significantly change the thicker bone, and also had significantly greater periosteal and endosteal osteoblast numbers compared to VAD-COD. Active osteoclasts were not detected in VAD rats, nor during the treatment period. These findings suggest that the abnormal bone thickness in VAD rats appears to be more effectively restored to bone thickness of untreated control rats when treated with COD.
Asunto(s)
Deficiencia de Vitamina A , Vitamina A , Animales , Aceite de Hígado de Bacalao , Ratas , Tretinoina/farmacología , Vitamina A/metabolismo , Deficiencia de Vitamina A/tratamiento farmacológico , Deficiencia de Vitamina A/metabolismoRESUMEN
A deficiency of vitamin A (VAD) and iron is the most common nutritional problem affecting people worldwide. Given the scale of the problem, the interactions between vitamin A and iron levels are widely studied. However, the exact mechanism of the impact of vitamin A on the regulation of iron metabolism remains unclear. An extremely significant issue becomes a better understanding of the nature of the studied biological phenomenon, which is possible by using a systems approach through developing and analyzing a mathematical model based on a Petri net. To study the considered system, the t-cluster analysis, the significance analysis, and the analysis of the average number of transition firings were performed. The used analyses have allowed distinguishing the most important mechanisms (both subprocesses and elementary processes) positively and negatively regulating an expression of hepcidin and allowed to distinguish elementary processes with a higher frequency of occurrence compared to others. The analysis also allowed to resolve doubts about the discrepancy in literature reports, where VAD leads to positive regulation of hepcidin expression or to negative regulation of hepcidin expression. The more detailed analyses have shown that VAD more frequently positively stimulates hepcidin expression and this mechanism is more significant than the mechanism inhibiting hepcidin expression indirectly by VAD.
Asunto(s)
Algoritmos , Anemia Ferropénica/metabolismo , Hepcidinas/metabolismo , Hierro/metabolismo , Análisis de Sistemas , Deficiencia de Vitamina A/metabolismo , Vitamina A/metabolismo , Anemia Ferropénica/complicaciones , Anemia Ferropénica/patología , Simulación por Computador , Humanos , Modelos Teóricos , Deficiencia de Vitamina A/complicaciones , Deficiencia de Vitamina A/patologíaRESUMEN
SCOPE: The effect of vitamin A deficiency on vitamin A and lipid postprandial metabolism in young rats is addressed, considering the effect of sex. METHODS AND RESULTS: Sprague-Dawley rats are fed either 400 UI.kg-1 vitamin A diet (vitamin A-deficient (VAD) diet) or 2300 UI.kg-1 vitamin A (control diet), before being mated. Mothers receive the same VAD or control diet during gestation and lactation. Offspring receive the same diet than mothers until 8 weeks of age. VAD diet-fed female and male offspring display a severe vitamin A deficiency with no body weight or glucose tolerance defects. Fasting plasma triglyceride concentrations are decreased in VAD diet-fed animals compared to controls (p < 0.05). Retinyl ester postprandial responses after vitamin A gavage, expressed as area under the curves, are not different in VAD diet-fed and control animals, although retinyl ester postprandial peak is significantly delayed (p < 0.05) in VAD diet-fed rats. Lipids also accumulate in the distal part of the intestine after gavage and [1-13 C]-oleate postprandial response is decreased in VAD diet-fed males. CONCLUSION: Vitamin A deficiency modulates both vitamin A absorption rate and lipid postprandial metabolism, which can partly explain the altered fasting lipid status observed in VAD diet-fed offspring.
Asunto(s)
Deficiencia de Vitamina A , Animales , Femenino , Metabolismo de los Lípidos , Hígado/metabolismo , Masculino , Ratas , Ratas Sprague-Dawley , Triglicéridos/metabolismo , Vitamina A/metabolismo , Deficiencia de Vitamina A/metabolismoRESUMEN
Increasing urbanization in developing countries has resulted in busier lifestyles, accompanied by consumption of fast foods. The consequence is an increased prevalence in noncommunicable diseases (NCDs). Food-based approaches would be cheaper and more sustainable in reducing these NCDs compared to drugs, which may have side effects. Studies have suggested that consuming functional foods could potentially lower NCD risks. Sweetpotato is regarded as a functional food because it contains bioactive compounds. Recently, sweetpotato has gained attention in sub-Saharan Africa (SSA), but research has focused on its use in alleviating micronutrient deficiencies such as vitamin A deficiency, particularly the orange-fleshed variety of sweetpotato. Some studies conducted in other parts of the world have investigated sweetpotato as a functional food. There is a need to characterize the sweetpotato varieties in SSA and determine how processing affects their bioactive components. This review highlights some of the studies conducted in various parts of the world on the functionality of sweetpotato, its bioactive compounds, and how these are influenced by processing. In addition, the potential health benefits imparted by sweetpotato are expounded. The knowledge gaps that remain in these studies are also addressed, focusing on how they can direct sweetpotato research in SSA.
Asunto(s)
Alimentos Funcionales/economía , Ipomoea batatas/metabolismo , África del Sur del Sahara/epidemiología , Agricultura/métodos , Alimentos Funcionales/provisión & distribución , Humanos , Fitoquímicos/metabolismo , Deficiencia de Vitamina A/metabolismo , Deficiencia de Vitamina A/terapiaRESUMEN
Motor dysfunctions are common comorbidities among autism spectrum disorder (ASD) patients. Abnormal cerebellar development throughout critical periods may have an effect on motor functions and result in motor impairments. Vitamin A (VA) plays a crucial role in the developing process of the nervous system. The correlation of VA deficiency (VAD) and ASD with motor dysfunctions, however, is not clear. Therefore, we built rat models with different VA levels based on the valproic acid (VPA)-treated autism model. ASD rats with VAD showed aggravated motor coordination abnormalities, Purkinje cell loss and impaired dendritic arborization of Purkinje cells compared to ASD rats with normal VA levels (VA normal, VAN). Additionally, the expression levels of retinoid-related orphan receptor α (RORα) and retinoic acid receptor α (RARα) were lower in the cerebellum of ASD rats with VAD than in those of ASD rats with VAN. VA supplementation (VAS) effectively improved motor coordination and cerebellar Purkinje cell abnormalities in ASD rats with VAD. Furthermore, the results of chromatin immunoprecipitation (ChIP) assays confirmed that the enrichment of RARα was detected on the RORα promoter in the cerebellum and that VAS could upregulate the binding capacity of RARα for RORα promoters. These results showed that VAD in autism might result in cerebellar impairments and be a factor aggravating a subtype of ASD with motor comorbidities. The therapeutic effect of VAS on motor deficits and Purkinje neuron impairments in autism might be due to the regulation of RORα by RARα.
Asunto(s)
Trastorno Autístico/metabolismo , Cerebelo/metabolismo , Miembro 1 del Grupo F de la Subfamilia 1 de Receptores Nucleares/metabolismo , Ácido Valproico/toxicidad , Deficiencia de Vitamina A/metabolismo , Vitamina A/administración & dosificación , Animales , Trastorno Autístico/inducido químicamente , Trastorno Autístico/tratamiento farmacológico , Cerebelo/efectos de los fármacos , Femenino , Masculino , Embarazo , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Efectos Tardíos de la Exposición Prenatal/tratamiento farmacológico , Efectos Tardíos de la Exposición Prenatal/metabolismo , Desempeño Psicomotor/efectos de los fármacos , Desempeño Psicomotor/fisiología , Ratas , Ratas Sprague-Dawley , Deficiencia de Vitamina A/tratamiento farmacológicoRESUMEN
Infection with high-risk human papillomavirus (HR-HPV) is the main cause of cervical cancer (CC), but viral infection alone does not guarantee the development of this malignancy. Indeed, deficiencies of dietary micronutrients could favor cervical cancer development in individuals that harbor HR-HPV infections. The status of retinoid levels, natural and synthetic derivatives of vitamin A, is important in maintaining cellular differentiation of the cervical epithelium. Moreover, many studies show a link between deficient intake of retinoids or alteration of the retinoid receptors and CC development. In spite of this, the effect of vitamin A deficiency (VAD) in presence of HR-HPV oncoproteins on cervical carcinogenesis in vivo has not been reported. Transgenic mice expressing E6 or E7 oncoproteins (K14E6 or K14E7 mice, respectively) were used to evaluate the possible role of VAD in the development of malignant cervical lesions. The survival of the mice in VAD condition was studied, and histopathological analysis and immunohistochemical detection of molecular cancer markers such as the tumor suppressor retinoic acid receptor beta (RARß), proliferating cell nuclear antigen (PCNA), cleaved caspase 3, and the tumor suppressor protein p16INK4A (inhibitor of CDK4) were performed. Our results show that K14E6/VAD mice showed moderate cervical dysplasia; notably, K14E7/VAD mice developed severe cervical dysplasia and cervical in situ carcinoma at an early age. VAD synergizes with HPV16E7 oncoprotein expression favoring cervical carcinogenesis in vivo.
Asunto(s)
Proteínas E7 de Papillomavirus/genética , Infecciones por Papillomavirus/patología , Neoplasias del Cuello Uterino/patología , Deficiencia de Vitamina A/complicaciones , Animales , Cuello del Útero/metabolismo , Cuello del Útero/patología , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , Progresión de la Enfermedad , Femenino , Humanos , Ratones , Ratones Transgénicos , Proteínas E7 de Papillomavirus/metabolismo , Infecciones por Papillomavirus/genética , Infecciones por Papillomavirus/metabolismo , Infecciones por Papillomavirus/virología , Antígeno Nuclear de Célula en Proliferación/genética , Antígeno Nuclear de Célula en Proliferación/metabolismo , Receptores de Ácido Retinoico/genética , Receptores de Ácido Retinoico/metabolismo , Neoplasias del Cuello Uterino/complicaciones , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/virología , Deficiencia de Vitamina A/genética , Deficiencia de Vitamina A/metabolismo , Deficiencia de Vitamina A/patologíaRESUMEN
Vitamin A deficiency can cause human pathologies that range from blindness to embryonic malformations. This diversity is due to the lack of two major vitamin A metabolites with very different functions: the chromophore 11-cis-retinal (vitamin A aldehyde) is a critical component of the visual pigment that mediates phototransduction, while the signaling molecule all-trans-retinoic acid regulates the development of various tissues and is required for the function of the immune system. Since animals cannot synthesize vitamin A de novo, they must obtain it either as preformed vitamin A from animal products or as carotenoid precursors from plant sources. Due to its essential role in the visual system, acute vitamin A deprivation impairs photoreceptor function and causes night blindness (poor vision under dim light conditions), while chronic deprivation results in retinal dystrophies and photoreceptor cell death. Chronic vitamin A deficiency is the leading cause of preventable childhood blindness according to the World Health Organization. Due to the requirement of vitamin A for retinoic acid signaling in development and in the immune system, vitamin A deficiency also causes increased mortality in children and pregnant women in developing countries. Drosophila melanogaster is an excellent model to study the effects of vitamin A deprivation on the eye because vitamin A is not essential for Drosophila development and chronic deficiency does not cause lethality. Moreover, genetic screens in Drosophila have identified evolutionarily conserved factors that mediate the production of vitamin A and its cellular uptake. Here, we review our current knowledge about the role of vitamin A in the visual system of mammals and Drosophila melanogaster. We compare the molecular mechanisms that mediate the uptake of dietary vitamin A precursors and the metabolism of vitamin A, as well as the consequences of vitamin A deficiency for the structure and function of the eye.
Asunto(s)
Visión Ocular/fisiología , Deficiencia de Vitamina A/fisiopatología , Vitamina A/metabolismo , Animales , Drosophila melanogaster/metabolismo , Mamíferos/metabolismo , Células Fotorreceptoras/metabolismo , Retina/metabolismo , Epitelio Pigmentado de la Retina/metabolismo , Retinaldehído/metabolismo , Tretinoina/metabolismo , Percepción Visual/fisiología , Vitamina A/fisiología , Deficiencia de Vitamina A/metabolismoRESUMEN
Vitamin A supplementation (VAS) in 6-59-month-old children is recommended but its sustainability is currently questioned. In Senegal, available data suggest that VAS should be maintained, but geographic and age-related specificities need to be addressed to better implement and target VAS programming. The objective of this comparative cross-sectional study, conducted in urban settings of Dakar, was to compare the vitamin A liver stores (VALS) assessed using the modified-relative dose response (MRDR) test between supplemented and non-supplemented 9-23 month-old children and to study their relationship with VAS. The supplemented group (n = 119) received VAS (either 100 000 UI or 200 000 UI) 2 to 6 months before evaluation while the non-supplemented group (n = 110) had not received VAS during the past 6 months. In addition to MRDR, serum retinol concentrations (SR), and biomarkers of subclinical inflammation were measured. Children's health-related data and feeding patterns were collected. Mean MRDR values (VAS: 0.030 ± 0.017, non-VAS: 0.028 ± 0.016, P = 0.389) and inflammation-adjusted SR (VAS: 1.34 ± 0.37, non-VAS: 1.3 ± 0.35, P = 0.515) of children were adequate. Low prevalence of VALS (VAS: 5.2%, non-VAS: 5.4%) and inflammation-adjusted VAD (VAS: 2.6%, non-VAS: 0.9%) were detected despite high presence of infections and inflammation. Children were mostly still being breastfed (VAS: 85.7%, non-VAS: 77.3%) and complementary feeding indicators were similar in both groups. Only breastfeeding was associated with VALS and was found to reduce by 76% at least, the odds of VAD (adjusted OR = 0.24, 95% CI: 0.07-0.8, P = 0.020). Based on MRDR values, VAS was not related to improved VALS and SR as well as VAD reduction among these children with adequate VALS. Reinforcing breastfeeding advocacy and morbidity prevention/control are essential in this setting. Scaling-back VAS in this subpopulation should be examined regarding the risk of hypervitaminosis A after an evaluation of dietary vitamin A intake sufficiency and a more quantitative assessment of VALS.
Asunto(s)
Lactancia Materna , Suplementos Dietéticos , Hígado/metabolismo , Población Urbana , Deficiencia de Vitamina A , Vitamina A , Estudios Transversales , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Lactante , Masculino , Senegal , Vitamina A/administración & dosificación , Vitamina A/farmacocinética , Deficiencia de Vitamina A/tratamiento farmacológico , Deficiencia de Vitamina A/metabolismoRESUMEN
Corneal and conjunctival inflammation and dry eye develop in systemic vitamin A deficiency (VAD). The objective of this study was to investigate the lacrimal ocular surface retinoid axis, particularly immunomodulatory effects of retinoic acid (RA) and change in conjunctival myeloid cell number and phenotype in VAD. We discovered that ocular surface epithelial and myeloid cells express retinoid receptors. Both all trans- and 9-cis-RA suppressed production of dry eye relevant inflammatory mediators [interleukin(IL)-1ß, IL-12, regulated upon activation, normal T cell expressed and secreted (RANTES)] by myeloid cells. Systemic VAD was associated with significant goblet cell loss and an increased number of CD45+ immune cells in the conjunctiva. MHCII-CD11b+ classical monocytes were significantly increased in the conjunctiva of VAD C57BL/6 and RXR-α mutated Pinkie strains. RNA seq revealed significantly increased expression of innate immune/inflammatory genes in the Pinkie conjunctiva. These findings indicate that retinoids are essential for maintaining a healthy, well-lubricated ocular surface and have immunomodulatory effects in the conjunctiva that are mediated in part via RXR-α signaling. Perturbation of the homeostatic retinoid axis could potentiate inflammation on the ocular surface.
Asunto(s)
Ojo/efectos de los fármacos , Inflamación/fisiopatología , Aparato Lagrimal/metabolismo , Retinoides/metabolismo , Animales , Quimiocina CCL5/metabolismo , Conjuntiva/metabolismo , Córnea/metabolismo , Síndromes de Ojo Seco/metabolismo , Femenino , Células Caliciformes/metabolismo , Homeostasis , Inmunidad Innata , Subunidad p35 de la Interleucina-12/metabolismo , Interleucina-1beta/metabolismo , Ratones , Ratones Endogámicos C57BL , Células Mieloides/metabolismo , Receptores de Ácido Retinoico/metabolismo , Transducción de Señal , Tretinoina/química , Vitamina A/metabolismo , Deficiencia de Vitamina A/metabolismoRESUMEN
AIMS: Vitamin A (VA) deficiency triggers many diseases and is a worldwide nutrition problem. The Retinol acyltransferase (LRAT) is an indicator of VA storage function, and the relationship between LRAT and blood pressure level and the regulation mechanism will be elucidated. METHODS: 160 children aged 6-12 years were included, and the serum VA and, the transcription levels of LRAT and RARs, were measured. Spontaneously hypertensive rats (SHRs) and WKY rats were treated with VA deficiency (VAD) or normal (VAN) fodder for 20 weeks. LRAT, retinoic acid, renin angiotensin system (RAS) biomarkers, and the structure and function of the heart for SHRs were measured. RESULTS: The serum retinol and serum retinol/BMI levels were lower in children in the low LRAT group (LRATAsunto(s)
Aciltransferasas/metabolismo
, Hipertensión
, Sistema Renina-Angiotensina
, Deficiencia de Vitamina A
, Vitamina A
, Animales
, Biomarcadores/metabolismo
, Presión Sanguínea/fisiología
, Niño
, Femenino
, Humanos
, Hipertensión/diagnóstico
, Hipertensión/tratamiento farmacológico
, Hipertensión/metabolismo
, Masculino
, Ratas
, Ratas Endogámicas SHR
, Sistema Renina-Angiotensina/efectos de los fármacos
, Sistema Renina-Angiotensina/fisiología
, Tretinoina/metabolismo
, Vitamina A/sangre
, Vitamina A/farmacología
, Deficiencia de Vitamina A/diagnóstico
, Deficiencia de Vitamina A/metabolismo
, Deficiencia de Vitamina A/terapia
, Vitaminas/sangre
, Vitaminas/farmacología
RESUMEN
This study presents two new concepts and definitions to the medical literature. One of those is "endogenous retinoic acid theory" and the other "retinoic acid depletion syndrome". A new classification will be provided for the immune system: "retinoic acid-dependent component" and "retinoic acid non-dependent component". If this theory is verified, all the diseases where the retinoic acid metabolism is defective and retinoic acid levels are low will be identified and new approaches will be developed fortreating such diseases. When the need for retinoic acids increases, such as acute infection, high fever, severe catabolic process, or chronic antigenic stimulation, cytochrome oxidase enzymes are inhibited by drugs or internal mechanisms. Metabolism and excretion of retinoic acids stored in the liver are prevented. In this way, retinoic acid levels in the blood are raised to therapeutic levels. This is called "Endogenous Retinoic Acid Theory". Retinoic acids also manage their metabolism through feedback mechanisms. Despite compensatory mechanisms, causes such as high fever, serious catabolic process and excessively large viral genome (SARS-CoV-2), excessive use of RIG-I and Type I interferon synthesis pathway using retinoic acid causes emptying of retinoic acid stores. As a result, the RIG-I pathway becomes ineffective, Type I IFN synthesis stops, and the congenital immune system collapses. Then the immune mechanism passes to TLR3, TLR7, TLR8, TLR9, MDA5 and UPS pathways in the monocyte, macrophage, neutrophil and dendritic cells of the adaptive immune defense system that do not require retinoic acid. This leads to excessive TNFα and cytokine discharge from the pathway. With the depletion of retinoic acid stores as a result of this overuse, the immune defense mechanism switches from the congenital immune system to the adaptive immune system, where retinoic acids cannot be used. As a result of this depletion of retinoic acids, the shift of the immune system to the NFκB arm, which causes excessive cytokine release, is called "retinoic acid depletion syndrome". COVID-19 and previously defined sepsis, SIRS and ARDS are each retinoic acid depletion syndrome. We claim that retinoic acid metabolism is defective in most inflammatory diseases, particularly COVID-19 (cytokine storm) sepsis, SIRS and ARDS. Finding a solution to this mechanism will bring a new perspective and treatment approach to such diseases.
Asunto(s)
COVID-19/inmunología , COVID-19/terapia , Tretinoina/metabolismo , Autoinmunidad , COVID-19/metabolismo , Carotenoides/metabolismo , Proteína 58 DEAD Box/inmunología , Humanos , Sistema Inmunológico , Interferón Tipo I/metabolismo , Interferones/metabolismo , Hígado/metabolismo , Modelos Teóricos , Sistema Nervioso/metabolismo , Receptores Inmunológicos , Síndrome , Carga Viral , Vitamina A/farmacología , Deficiencia de Vitamina A/metabolismo , Zinc/metabolismoRESUMEN
Fatty acid translocase (CD36) is a scavenger receptor with multiple ligands and diverse physiological actions. We recently reported that alcohol-induced hepatic retinoid mobilization is impaired in Cd36-/- mice, leading us to hypothesize that CD36 has a novel role in hepatic vitamin A mobilization. Given the central role of the liver in systemic vitamin A homeostasis we also postulated that absence of CD36 would affect whole-body vitamin A homeostasis. We tested this hypothesis in aging wild type and Cd36-/- mice, as well as mice fed a vitamin A-deficient diet. In agreement with our hypothesis, Cd36-/- mice accumulated hepatic retinyl ester stores with age to a greater extent than wild type mice. However, contrary to expectations, Cd36-/- mice consuming a vitamin A-deficient diet mobilized hepatic retinoid similar to wild type mice. Interestingly, we observed that Cd36-/- mice had significantly reduced white adipose tissue retinoid levels compared to wild type mice. In conclusion, we demonstrate that the absence of CD36 alters whole-body vitamin A homeostasis and suggest that this phenotype is secondary to the impaired chylomicron metabolism previously reported in these mice.
Asunto(s)
Envejecimiento/metabolismo , Antígenos CD36/deficiencia , Homeostasis/genética , Hígado/metabolismo , Deficiencia de Vitamina A/metabolismo , Vitamina A/metabolismo , Aciltransferasas/genética , Aciltransferasas/metabolismo , Tejido Adiposo Blanco/metabolismo , Tejido Adiposo Blanco/patología , Envejecimiento/genética , Animales , Peso Corporal , Antígenos CD36/genética , Quilomicrones/metabolismo , Regulación de la Expresión Génica , Hígado/patología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Tamaño de los Órganos , Receptores de Ácido Retinoico/genética , Receptores de Ácido Retinoico/metabolismo , Ácido Retinoico 4-Hidroxilasa/genética , Ácido Retinoico 4-Hidroxilasa/metabolismo , Proteínas Celulares de Unión al Retinol/genética , Proteínas Celulares de Unión al Retinol/metabolismo , Ésteres de Retinilo/metabolismo , Deficiencia de Vitamina A/genética , Deficiencia de Vitamina A/patologíaRESUMEN
This study was carried out to investigate the effects of dietary vitamin A (VA) on growth performance, antioxidant capacity, digestion, intestinal immune response, and mRNA expression of intestinal tight junction proteins for juvenile hybrid grouper (Epinephelus fuscoguttatus â × Epinephelus lanceolatus â). Six isonitrogenous and isolipidic experimental diets were formulated to obtain VA levels (317, 1136, 2038, 4142, 7715, 15204 IU/kg diet, respectively). The triplicate groups of fish (average weight of 9.01 ± 0.27 g) were fed twice daily (8:00 and 16:00) for 7 weeks. Based on the broken-line analysis model of WG and LYZ activity, the dietary VA requirement of hybrid grouper were estimated to be 2688.58 and 4096.36 IU/kg diet. The results showed that VA deficiency or excess could reduce Weight gain, specific growth rate, and protein efficiency ratio, and increase feed conversion ratio and hepatosomatic index (P < 0.05). In addition, VA deficiency could reduce the serum activities of acid phosphatase (ACP), superoxide dismutase, and total antioxidant capacity and increase the malondialdehyde content (P < 0.05). VA deficiency also could reduce intestinal activities of ACP, alkaline phosphatase, lysozyme, complement 3, complement 4 contents, and activities of alpha-amylase, lipase, and trypsin (P < 0.05). Meanwhile, VA deficiency could reduce villus height in proximal intestine (PI) and mid intestine (MI), as well as muscle thickness in PI and distal intestine (DI) (P < 0.05). Moreover, VA deficiency could down-regulated antimicrobial peptides (ß-defensin, Hepcidin [not in MI and DI], Epinecidin), anti-inflammatory cytokines (interleukin 10 and transforming growth factor ß1 [not in DI]), tight junction proteins (occluding and claudin3) mRNA levels in the PI, MI and DI, and up-regulated pro-inflammatory cytokines (tumor necrosis factor α [not in MI] and interleukin 1ß [not in MI]), signaling molecules c-Rel and p65 (P < 0.05). Collectively, VA deficiency could reduce growth performance because of a negative effect on intestinal health by depressing digestive abilities, intestinal morphology, immunity and tight junction function in the intestine.