Bridging the vitamin A and deworming coverage gap among underserved populations in India through government and civil society organization partnerships.

BACKGROUND: Vitamin A deficiency (VAD) is a major public health problem in India, where approximately 62% of children under five have low retinol levels (< 70 µmol/L). This study aims to (1) evaluate vitamin A supplementation (VAS) and deworming (VAS + D) coverage in Nagaland state through government and civil society organization (CSO) partnerships, (2) examine socio-demographic barriers and facilitators to VAS + D coverage, (3) examine associations between socio-demographic characteristics and source of VAS coverage (i.e., government vs. CSOs), and (4) estimate the impact of VAS on health outcomes due to increased coverage through government and CSO partnerships. METHODS: A cross-sectional statewide coverage survey was conducted in Nagaland, India with 1,272 caregivers of children 6-59 months. Household socio-demographic data and VAS + D exposure variables were collected via quantitative survey. Univariate analyses were used to assess the associations between the independent and outcome variables; odds ratios were computed to measure the strength of the association at a significance level of < 0.05. The Lives Saved Tool (LiST) was used to estimate the impact of increased VAS coverage on child undernutrition, morbidity and mortality. RESULTS: Most children (77.2%) received VAS in the past six months, with 28.1% receiving VAS in capsule form (provided primarily by CSOs) and 70.2% received VAS in syrup form (provided primarily by government). Total deworming coverage was 74.2%, with 43.5% receiving both VAS and deworming. Lower pre-school enrollment was a barrier to receiving VAS (47.4% not enrolled vs. 80.9% enrolled, p < 0.001). A barrier to receiving VAS + D was lack of knowledge of benefits (p < 0.001). Based on LiST modeling, increasing VAS coverage by 22% through CSOs resulted in an estimated 114 stunting cases averted, 25,017 diarrhea cases averted, and 9 lives saved in 2019 in Nagaland State. CONCLUSIONS: Government and CSO partnerships can reduce disparities in VAS coverage and decrease under-five child morbidity and mortality.

Retinoic acid signalling inhibits myogenesis by blocking MYOD translation in pig skeletal muscle cells.

Vitamin A is an essential nutrient in animals, playing important roles in animal health. In the pig industry, proper supplementation of vitamin A in the feed can improve pork production performance, while deficiency or excessive intake can lead to growth retardation or disease. However, the specific molecular mechanisms through which vitamin A operates on pig skeletal muscle growth as well as muscle stem cell function remain unexplored. Therefore, in this study, we isolated the pig primary skeletal muscle stem cells (pMuSCs) and treated with retinoic acid (RA), the natural metabolite of vitamin A, and then examined the myogenic capacity of pMuSCs via immunostaining, real-time PCR, CCK8 and western-blot analysis. Unexpectedly, the RA caused a significant decrease in the proliferation and differentiation of pMuSCs. Mechanistically, the RA addition induced the activation of retinoic acid receptor gamma (RARγ), which inhibited the myogenesis through the blockage of protein translation of the master myogenic regulator myogenic differentiation 1 gene (MYOD). Specifically, RARγ inactivate AKT kinase (AKT) signalling and lead to dephosphorylation of eukaryotic translation initiation factor 4E binding protein 1 (eIF4EBP1), which in turn repress the eukaryotic translation initiation factor 4E (eIF4E) complex and block mRNA translation of MYOD. Inhibition of AKT could rescue the myogenic defects of RA-treated pMuSCs. Our findings revealed that retinoid acid signalling inhibits the skeletal muscle stem cell proliferation and differentiation in pigs. Therefore, the vitamin A supplement in the feedstuff should be cautiously optimized to avoid the potential adverse consequences on muscle development associated with the excessive levels of retinoic acid.

Knowledge and attitudes about vitamin A consumption and its relationship with night blindness in university students.

Introduction: Night blindness is the first sign of vitamin A deficiency (VAD), which can lead to blindness if left untreated. University students may be at risk of VAD-related night blindness due to unhealthy eating attitudes and inadequate vitamin A intake. This study aimed to determine the relationship between knowledge and attitudes toward vitamin A consumption affecting night blindness in university students. Methods: This cross-sectional study involved 409 third-year university students of Universitas Islam Sultan Agung, Semarang, Indonesia. Participants completed questionnaires about socio-demographics, their knowledge of vitamin A, and attitudes toward vitamin A consumption. Night blindness symptoms among university students were assessed using the Low Luminance Questionnaire (LLQ), followed by a bivariate analysis of the Chi-Square test. Multivariate binary logistic regressions were used to determine whether the independent variables were associated with night blindness. A p-value less than 0.05 indicated significance. Results: The prevalence of high-symptom night blindness was higher among males (26.4%) than females (5.7%). Out of 409 university students, 48 from the non-medicine cluster of the study program had a night blindness symptom. The prevalence was lower in students who studied in the medicine cluster program. The level of knowledge on vitamin A had a significant relationship with symptoms of night blindness [prevalence ratio (PR) = 2.239 (95% CI = 1.110-4.516)]. The attitudes toward vitamin A consumption were significantly associated with night blindness (PR = 2.560, 95% CI = 1.215-5.392). Discussion: The results of this study show that the risk of night blindness in university students can be prevented by increasing their knowledge and attitudes toward consuming vitamin A-rich food. The university can provide health promotion and vitamin A supplementation to avoid night blindness among academia.

The role of vitamins and nutrients in rosacea.

Rosacea is a common inflammatory skin condition displaying symptoms like flushing, erythema, papules, and pustules. Oral antibiotics, despite long-term adverse effects, are often used due to topical treatment limitations, underscoring the need for cost-effective choices like dietary modifications. Our review investigates the role of vitamins and minerals in rosacea, and provides evidence-based recommendations for supplementation and topical treatment of these nutrients for rosacea. An online search was performed on PubMed, Web of Science, Science Direct, Google Scholar, and ClinicalTrials.gov from 1998 to 2023. Included studies were summarized and assessed for quality and relevance in rosacea management. Varied outcomes emerged concerning the impact of essential vitamins and minerals on rosacea treatment. Vitamin A derivatives, specifically oral isotretinoin, demonstrated significant efficacy, with a 90% reduction in lesions, complete remission in 24% of patients, and marked improvement in 57% of patients. Vitamin B3 derivatives, such as topical 1-methylnicotinamide 0.25% and NADH 1%, improved symptoms in 76.4% (26/34) and 80% of patients, respectively. Outcomes for vitamin D, vitamin C, and zinc supplementation varied across studies. However, zinc sulfate solution 5% significantly reduced acne rosacea severity for patients with 40% and 60% exhibiting a moderate or good response, respectively. Omega-3 fatty acids showed significant improvement in alleviating xerophthalmia in 64% of patients with ocular rosacea. Vitamins and minerals hold potential in managing rosacea symptoms, offering a safe and cost-effective alternative or adjunctive treatment option. Currently, there are no established recommendations regarding their supplementation for rosacea. Studies assessing serum levels of vitamins and minerals in relation to rosacea are warranted, as this avenue holds potential for future advancements in the field.

Association between serum vitamin A and body mass index in adolescents from NHANES 1999 to 2006.

Vitamin A plays a pivotal role in health, particularly in regulating fat metabolism. Despite its significance, research into the direct relationship between vitamin A levels and obesity, especially among adolescents, is sparse. This study aims to explore this association within the adolescent population in the United States. This cross-sectional study analyzed the National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2006, with 8218 participants. The levels of vitamin A in the serum were determined based on utilizing high-performance liquid chromatography with photodiode array detection. The relationship between serum vitamin A concentrations and body mass index (BMI) was evaluated using weighted multiple linear regression models, incorporating subgroup analyses by sex and race/ethnicity to provide nuanced insights. A positive correlation was observed between serum vitamin A levels and BMI, with BMI increasing progressively across vitamin A quartiles (P < 0.001). Using the lowest quartile of serum vitamin A as a reference, the BMI of the highest quartile of serum vitamin A was 1.236 times higher (95% CI 0.888, 1.585). Subgroup analyses revealed that this positive association persisted across different genders and racial/ethnic groups (P < 0.001). Notably, smooth curve fitting and saturation threshold analysis unveiled an inverted U-shaped relationship between serum vitamin A and BMI among female adolescents, non-Hispanic Whites, Mexican Americans, and other races/ethnicities groups. Our study substantiates the association between serum vitamin A levels and the risk of obesity/overweight status in adolescents. The findings suggest the potential serum vitamin A is an early biomarker for identifying obesity risk, although further studies are needed to determine to clarify its role as a contributing factor to obesity. This study contributes to the understanding of nutritional influences on adolescent obesity, highlighting the need for targeted interventions based on serum biomarkers.

Dietary micronutrients intake and its effect on haemoglobin levels of pregnant women for clinic visit in the Mount Cameroon health area: a cross-sectional study.

Background: Nutritional deficiencies and its consequences such as anaemia are frequent among pregnant women residing in under resource settings. Hence, this study sought to investigate specific dietary micronutrient inadequacy and its effect on maternal haemoglobin levels. Methods: This institution based cross-sectional survey enrolled 1,014 consenting pregnant women consecutively. Data on socio-demographic, economic and antenatal characteristics were recorded using a structured questionnaire. Minimum dietary diversity for women (MDD-W) was assessed using the 24-h recall method and haemoglobin (Hb) concentration (g/dL) determined using a portable Hb metre. Significant levels between associations was set at p < 0.05. Results: Among those enrolled, 40.9% were anaemic while 89.6% had inadequate dietary nutrient intake. In addition, uptake of blood supplements, haem iron, plant and animal-based foods rich in vitamin A were 71.5, 86.2, 35.5 and 12.6%, respectively. Moreover, anaemia prevalence was significantly (p < 0.05) lower in women who took iron-folic acid along with food groups rich in haem iron (38.5%) or both plant and animal vitamin A (29.0%). Besides, mean maternal Hb levels was significantly (p < 0.001) higher in women who consumed haem iron (11.08 ± 1.35) and vitamin A food groups (11.34 ± 1.30) when compared with their counterparts who did not consume haem iron (10.54 ± 1.19) and vitamin A food groups (10.74 ± 1.31). Conclusion: Dietary uptake of foods rich in haem-iron and vitamin A significantly improves Hb levels in Cameroonian pregnant women. Our findings underscore the importance of improving maternal nutritional awareness and counselling during antenatal period to reduce the anaemia burden.

Early Life Programming of Adipose Tissue Remodeling and Browning Capacity by Micronutrients and Bioactive Compounds as a Potential Anti-Obesity Strategy.

The early stages of life, especially the period from conception to two years, are crucial for shaping metabolic health and the risk of obesity in adulthood. Adipose tissue (AT) plays a crucial role in regulating energy homeostasis and metabolism, and brown AT (BAT) and the browning of white AT (WAT) are promising targets for combating weight gain. Nutritional factors during prenatal and early postnatal stages can influence the development of AT, affecting the likelihood of obesity later on. This narrative review focuses on the nutritional programming of AT features. Research conducted across various animal models with diverse interventions has provided insights into the effects of specific compounds on AT development and function, influencing the development of crucial structures and neuroendocrine circuits responsible for energy balance. The hormone leptin has been identified as an essential nutrient during lactation for healthy metabolic programming against obesity development in adults. Studies have also highlighted that maternal supplementation with polyunsaturated fatty acids (PUFAs), vitamin A, nicotinamide riboside, and polyphenols during pregnancy and lactation, as well as offspring supplementation with myo-inositol, vitamin A, nicotinamide riboside, and resveratrol during the suckling period, can impact AT features and long-term health outcomes and help understand predisposition to obesity later in life.

Vitamin A - discovery, metabolism, receptor signaling and effects on bone mass and fracture susceptibility.

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.

Uncommon opsin's retinal isomer is involved in mammalian sperm thermotaxis.

In recent years it became apparent that, in mammals, rhodopsin and other opsins, known to act as photosensors in the visual system, are also present in spermatozoa, where they function as highly sensitive thermosensors for thermotaxis. The intriguing question how a well-conserved protein functions as a photosensor in one type of cells and as a thermosensor in another type of cells is unresolved. Since the moiety that confers photosensitivity on opsins is the chromophore retinal, we examined whether retinal is substituted in spermatozoa with a thermosensitive molecule. We found by both functional assays and mass spectrometry that retinal is present in spermatozoa and required for thermotaxis. Thus, starvation of mice for vitamin A (a precursor of retinal) resulted in loss of sperm thermotaxis, without affecting motility and the physiological state of the spermatozoa. Thermotaxis was restored after replenishment of vitamin A. Using reversed-phase ultra-performance liquid chromatography mass spectrometry, we detected the presence of retinal in extracts of mouse and human spermatozoa. By employing UltraPerformance convergence chromatography, we identified a unique retinal isomer in the sperm extracts-tri-cis retinal, different from the photosensitive 11-cis isomer in the visual system. The facts (a) that opsins are thermosensors for sperm thermotaxis, (b) that retinal is essential for thermotaxis, and (c) that tri-cis retinal isomer uniquely resides in spermatozoa and is relatively thermally unstable, suggest that tri-cis retinal is involved in the thermosensing activity of spermatozoa.

Adipocyte HSL is required for maintaining circulating vitamin A and RBP4 levels during fasting.

Vitamin A (retinol) is distributed via the blood bound to its specific carrier protein, retinol-binding protein 4 (RBP4). Retinol-loaded RBP4 is secreted into the circulation exclusively from hepatocytes, thereby mobilizing hepatic retinoid stores that represent the major vitamin A reserves in the body. The relevance of extrahepatic retinoid stores for circulating retinol and RBP4 levels that are usually kept within narrow physiological limits is unknown. Here, we show that fasting affects retinoid mobilization in a tissue-specific manner, and that hormone-sensitive lipase (HSL) in adipose tissue is required to maintain serum concentrations of retinol and RBP4 during fasting in mice. We found that extracellular retinol-free apo-RBP4 induces retinol release by adipocytes in an HSL-dependent manner. Consistently, global or adipocyte-specific HSL deficiency leads to an accumulation of retinoids in adipose tissue and a drop of serum retinol and RBP4 during fasting, which affects retinoid-responsive gene expression in eye and kidney and lowers renal retinoid content. These findings establish a novel crosstalk between liver and adipose tissue retinoid stores for the maintenance of systemic vitamin A homeostasis during fasting.

A Chemical Structure and Machine Learning Approach to Assess the Potential Bioactivity of Endogenous Metabolites and Their Association with Early Childhood Systemic Inflammation.

Metabolomics has gained much attention due to its potential to reveal molecular disease mechanisms and present viable biomarkers. This work uses a panel of untargeted serum metabolomes from 602 children from the COPSAC2010 mother-child cohort. The annotated part of the metabolome consists of 517 chemical compounds curated using automated procedures. We created a filtering method for the quantified metabolites using predicted quantitative structure-bioactivity relationships for the Tox21 database on nuclear receptors and stress response in cell lines. The metabolites measured in the children's serums are predicted to affect specific targeted models, known for their significance in inflammation, immune function, and health outcomes. The targets from Tox21 have been used as targets with quantitative structure-activity relationships (QSARs). They were trained for ~7000 structures, saved as models, and then applied to the annotated metabolites to predict their potential bioactivities. The models were selected based on strict accuracy criteria surpassing random effects. After application, 52 metabolites showed potential bioactivity based on structural similarity with known active compounds from the Tox21 set. The filtered compounds were subsequently used and weighted by their bioactive potential to show an association with early childhood hs-CRP levels at six months in a linear model supporting a physiological adverse effect on systemic low-grade inflammation.

Retinoic acid modulation of granule cell activity and spatial discrimination in the adult hippocampus.

Retinoic acid (RA), derived from vitamin A (retinol), plays a crucial role in modulating neuroplasticity within the adult brain. Perturbations in RA signaling have been associated with memory impairments, underscoring the necessity to elucidate RA's influence on neuronal activity, particularly within the hippocampus. In this study, we investigated the cell type and sub-regional distribution of RA-responsive granule cells (GCs) in the mouse hippocampus and delineated their properties. We discovered that RA-responsive GCs tend to exhibit a muted response to environmental novelty, typically remaining inactive. Interestingly, chronic dietary depletion of RA leads to an abnormal increase in GC activation evoked by a novel environment, an effect that is replicated by the localized application of an RA receptor beta (RARß) antagonist. Furthermore, our study shows that prolonged RA deficiency impairs spatial discrimination-a cognitive function reliant on the hippocampus-with such impairments being reversible with RA replenishment. In summary, our findings significantly contribute to a better understanding of RA's role in regulating adult hippocampal neuroplasticity and cognitive functions.

Neonatal vitamin A supplementation improves sheep fertility potential.

This study aimed to explore the effects of neonatal vitamin A (VA) supplementation on testis development and spermatogenesis. A total of 32 newborn lambs were intramuscularly injected with corn oil (control group) or corn oil + 2500 IU/kg BW VA (VA group). They were slaughtered and sampled at 3 weeks and 8 months of age to analyze spermatogenesis, cell proliferation, hormone secretion, antioxidant status of the testis, and adult sheep sperm parameters. Compared with the control group, the expression of spermatogonial differentiation-related genes in VA group was up-regulated (P < 0.05). Testis weight, seminiferous tubule diameter, number of spermatogonium and spermatocyte, and sperm density increased significantly in VA group at 8 months of age (P < 0.05). Neonatal VA injection upregulated the expression of the cell proliferation marker PCNA and cell cycle-related genes in the testis (P < 0.05). VA increased the concentrations of testosterone (T), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) in the serum and upregulated steroidogenesis-related genes in the testis (P < 0.05). The antioxidant levels in the VA group were maintained at high levels. The total antioxidant capacity (T-AOC), antioxidant enzyme content and antioxidant-related genes were increased in the testis (P < 0.05). Furthermore, neonatal VA injection activated retinoic acid (RA) signaling to maintain the blood-testosterone barrier (BTB) in the testis of 3-week-old sheep. AMP-activated protein kinase (AMPK) and protein kinase B (AKT) signaling were also modulated in the sheep testis (P < 0.05). Taken together, VA supplementation in newborn rams promotes testis development and spermatogenesis to improve fertility.

Quantification of Vitamin A in Edible Oils: Comparison of Portable Device iCheck Chroma3 to High-Performance Liquid Chromatography.

Fortification of edible oil with vitamin A is a widely adopted intervention to minimize the effects of vitamin A deficiency in vulnerable groups and mitigate some of its deleterious consequences. Regulatory monitoring is an important prerequisite to ensure that the fortification program is implemented effectively. Standard laboratory analysis methods for vitamin A in oils to assess adequate addition levels remain expensive and time-consuming. Portable testing devices are relatively less expensive in terms of capital investment and cost per test. However, the reliability of results needs to be assured to ensure acceptability and confidence. This study compared a portable device to high-performance liquid chromatography (HPLC) in terms of quantification of vitamin A in both spiked and commercially fortified oils. Nine oils (soybean, palm, cottonseed, rapeseed, corn, peanut, coconut, sunflower, and rice bran oils) were selected and spiked with retinyl palmitate at six different concentrations, and 112 commercially fortified oils were quantified for their vitamin A content using both methods. A good indicator of intra-day and inter-day repeatability (< 10% CV) was obtained for the measurement of vitamin A in the spiked oils for both methods, which denotes a high agreement between them. Vitamin A recoveries were 97-132% for HPLC and 74-127% for the portable device. A strong positive correlation, r = 0.88, is observed between the two methods for the quantification of vitamin A in the commercially fortified oils. The portable device provides a relatively low-cost, quick, and user-friendly alternative to HPLC.

Retinol and retinol binding protein 4 levels and COVID-19: a Mendelian randomization study.

BACKGROUND: The Corona Virus Disease 2019 (COVID-19) pandemic has struck globally. Whether the related proteins of retinoic acid (RA) signaling pathway are causally associated with the risk of COVID-19 remains unestablished. We conducted a two-sample Mendelian randomization (MR) study to assess the associations of retinol, retinol binding protein 4 (RBP4), retinol dehydrogenase 16 (RDH16) and cellular retinoic acid binding protein 1 (CRABP1) with COVID-19 in European population. METHODS: The outcome utilized the summary statistics of COVID-19 from the COVID-19 Host Genetics Initiative. The exposure data were obtained from public genome wide association study (GWAS) database. We extracted SNPs from exposure data and outcome data. The inverse variance weighted (IVW), MR-Egger and Wald ratio methods were employed to assess the causal relationship between exposure and outcome. Sensitivity analyses were performed to ensure the validity of the results. RESULTS: The MR estimates showed that retinol was associated with lower COVID-19 susceptibility using IVW (OR: 0.69, 95% CI: 0.53-0.90, P: 0.0065), whereas the associations between retinol and COVID-19 hospitalization or severity were not significant. RBP4 was associated with lower COVID-19 susceptibility using the Wald ratio (OR: 0.83, 95% CI: 0.72-0.95, P: 0.0072). IVW analysis showed RDH16 was associated with increased COVID-19 hospitalization (OR: 1.10, 95% CI: 1.01-1.18, P: 0.0199). CRABP1 was association with lower COVID-19 susceptibility (OR: 0.95, 95% CI: 0.91-0.99, P: 0.0290) using the IVW. CONCLUSIONS: We found evidence of possible causal association of retinol, RBP4, RDH16 and CRABP1 with the susceptibility, hospitalization and severity of COVID-19. Our study defines that retinol is significantly associated with lower COVID-19 susceptibility, which provides a reference for the prevention of COVID-19 with vitamin A supplementation.

The Logistical Backbone of Photoreceptor Cell Function: Complementary Mechanisms of Dietary Vitamin A Receptors and Rhodopsin Transporters.

In this review, we outline our current understanding of the mechanisms involved in the absorption, storage, and transport of dietary vitamin A to the eye, and the trafficking of rhodopsin protein to the photoreceptor outer segments, which encompasses the logistical backbone required for photoreceptor cell function. Two key mechanisms of this process are emphasized in this manuscript: ocular and systemic vitamin A membrane transporters, and rhodopsin transporters. Understanding the complementary mechanisms responsible for the generation and proper transport of the retinylidene protein to the photoreceptor outer segment will eventually shed light on the importance of genes encoded by these proteins, and their relationship on normal visual function and in the pathophysiology of retinal degenerative diseases.

Potentials and limitations of a food group-based algorithm to assess dietary nutrient intake of women in rural areas in Tanzania.

The aim of this study was to evaluate the accuracy of nutrient intake assessment with the food group-based algorithm "Calculator of Inadequate Micronutrient Intake" (CIMI) in comparison to the established nutrition software NutriSurvey. Using Food Frequency Questionnaires and 24-h dietary recalls of 1010 women from two rural districts in Tanzania, 23 relevant typical Tanzanian food groups were identified and subsequently the dietary protocols assessed via CIMI algorithm were compared by bivariate correlations and Bland-Altman analysis with the results of the NutriSurvey software (reference) and were set in relation to blood biomarkers of 666 participants. CIMI and NutriSurvey calculations regarding macro- and micronutrient intakes were similar. The Bland-Altman analyses and correlation coefficients of energy (0.931), protein (0.898), iron (0.775) and zinc (0.838) confirm the agreement of both calculations. The food group based CIMI algorithm is a practical tool to identify the inadequacy of macro- and micronutrient intake at population level.

Modest effect of differential dietary vitamin A intake on the pathogenesis of alcohol-associated liver disease.

BACKGROUND: Chronic alcohol consumption is a major public health issue. The primary organ damaged by alcohol abuse is the liver, leading to alcohol-associated liver disease (ALD). ALD begins with hepatic steatosis and can progress to fibrosis and cirrhosis; however, we have an incomplete understanding of ALD pathogenesis. Interestingly, the liver is also the major organ for vitamin A metabolism and storage, and ALD has previously been linked with altered hepatic vitamin A homeostasis. We hypothesize that alcohol-induced vitamin A depletion disrupts its normal function in the liver, contributing to the pathogenesis of ALD. To test this hypothesis, we postulated that adding copious vitamin A to the diet might alleviate ALD, and conversely, that a vitamin A deficient diet would worsen ALD. METHODS: We conducted two dietary intervention studies in mice comparing deficient (0 IU/g diet) and copious (25 IU/g diet) dietary vitamin A intake versus control (4 IU/g diet), using the NIAAA chronic-binge model of ALD. Hepatic steatosis was assessed using histopathological and biochemical approaches. Tissue Vitamin A levels were measured using high-performance liquid chromatography. Markers of ALD, hepatic inflammation and lipid metabolism were analyzed by the quantitative polymerase chain reaction and western blotting. RESULTS: As expected, a 0 IU/g Vitamin A diet decreased, and a 25 IU/g Vitamin A diet increased hepatic Vitamin A stores. However, alcohol induced changes in hepatic triglyceride levels, markers of hepatic lipid metabolism, inflammation and fibrosis were not significantly different in mice consuming a copious or deficient vitamin A diet compared to control. CONCLUSIONS: Altered vitamin A intake and hepatic vitamin A storage have a minor effect on the pathogenesis of ALD. Thus, given the known link between altered retinoic acid signaling and ALD, future studies that further explore this linkage are warranted.

Vitamin A-treated natural killer cells reduce interferon-gamma production and support regulatory T-cell differentiation.

Natural killer (NK) cells are innate cytotoxic lymphocytes that contribute to immune responses against stressed, transformed, or infected cells. NK cell effector functions are regulated by microenvironmental factors, including cytokines, metabolites, and nutrients. Vitamin A is an essential micronutrient that plays an indispensable role in embryogenesis and development, but was also reported to regulate immune responses. However, the role of vitamin A in regulating NK cell functions remains poorly understood. Here, we show that the most prevalent vitamin A metabolite, all-trans retinoic acid (atRA), induces transcriptional and functional changes in NK cells leading to altered metabolism and reduced IFN-γ production in response to a wide range of stimuli. atRA-exposed NK cells display a reduced ability to support dendritic cell (DC) maturation and to eliminate immature DCs. Moreover, they support the polarization and proliferation of regulatory T cells. These results imply that in vitamin A-enriched environments, NK cells can acquire functions that might promote tolerogenic immunity and/or immunosuppression.

Early-life vitamin A treatment rescues neonatal infection-induced durably impaired tolerogenic properties of celiac lymph nodes.

Gut-draining mesenteric and celiac lymph nodes (mLNs and celLNs) critically contribute to peripheral tolerance toward food and microbial antigens by supporting the de novo induction of regulatory T cells (Tregs). These tolerogenic properties of mLNs and celLNs are stably imprinted within stromal cells (SCs) by microbial signals and vitamin A (VA), respectively. Here, we report that a single, transient gastrointestinal infection in the neonatal, but not adult, period durably abrogates the efficient Treg-inducing capacity of celLNs by altering the subset composition and gene expression profile of celLNSCs. These cells carry information about the early-life pathogen encounter until adulthood and durably instruct migratory dendritic cells entering the celLN with reduced tolerogenic properties. Mechanistically, transiently reduced VA levels cause long-lasting celLN functional impairment, which can be rescued by early-life treatment with VA. Together, our data highlight the therapeutic potential of VA to prevent sequelae post gastrointestinal infections in infants.