scholarly journals Vitamin A deficiency affects gene expression in the Drosophila melanogaster head

2021 ◽  
Author(s):  
Deepshe Dewett ◽  
Maryam Labaf ◽  
Khanh Lam-Kamath ◽  
Kourosh Zarringhalam ◽  
Jens Rister
Keyword(s):  
Gene Expression ◽  
Drosophila Melanogaster ◽  
Vitamin A ◽  
Molecular Mechanisms ◽  
Vitamin A Deficiency ◽  
Light Stress ◽  
Light Response ◽  
Developmental Defects ◽  
Increased Risk ◽  
Retinal Chromophore

Abstract Insufficient dietary intake of vitamin A causes various human diseases. For instance, chronic vitamin A deprivation causes blindness, slow growth, impaired immunity, and an increased risk of mortality in children. In contrast to these diverse effects of vitamin A deficiency (VAD) in mammals, chronic VAD in flies neither causes obvious developmental defects nor lethality. As in mammals, VAD in flies severely affects the visual system: it impairs the synthesis of the retinal chromophore, disrupts the formation of the visual pigments (Rhodopsins), and damages the photoreceptors. However, the molecular mechanisms that respond to VAD remain poorly understood. To identify genes and signaling pathways that are affected by VAD, we performed RNA-sequencing and differential gene expression analysis in Drosophila melanogaster. We found an upregulation of genes that are essential for the synthesis of the retinal chromophore, specific aminoacyl-tRNA synthetases, and major nutrient reservoir proteins. We also discovered that VAD affects several genes that are required for the termination of the light response: for instance, we found a downregulation of both arrestin genes that are essential for the inactivation of Rhodopsin. A comparison of the VAD-responsive genes with previously identified blue light stress-responsive genes revealed that the two types of environmental stress trigger largely nonoverlapping transcriptome responses. Yet, both stresses increase the expression of seven genes with poorly understood functions. Taken together, our transcriptome analysis offers insights into the molecular mechanisms that respond to environmental stresses.

scholarly journals 244.Interaction between bone morphogenetic protein 4 and retinoid signalling in mouse spermatogenesis

2004 ◽  
Vol 16 (9) ◽  
pp. 244
Author(s):  
R. M. Baleato ◽  
R. J. Aitken ◽  
S. D. Roman
Keyword(s):  
Gene Expression ◽  
Vitamin A ◽  
Bone Morphogenetic Protein ◽  
Germ Cells ◽  
Molecular Mechanisms ◽  
Vitamin A Deficiency ◽  
Morphogenetic Protein ◽  
Bmp4 Expression ◽  
High Doses

Vitamin A (retinol, or ROL) is also essential for normal spermatogenesis in the rat and mouse. Vitamin A-deficient (VAD) rodents suffer various disorders including blindness and male infertility. The molecular mechanisms leading to infertility in vitamin A deficient rodents have never been fully elucidated. Following prolonged vitamin A withdrawal the only germ cells remaining in the VAD rodent testis are stem cell spermatogonia, type A1 spermatogonia, and a few preleptotene spermatocytes. Supplementing the diet of these animals with retinoic acid (RA) alleviates all symptoms of vitamin A deficiency, with the exception of sight and spermatogenesis. It is not until VAD animals are re-administered ROL through the diet, or RA is injected in repeated high doses directly into the testis, that normal spermatogenic function is restored. Here we report an interaction, in germ cells, between the Bone Morphogenetic Protein (BMP) 4 and retinoid signalling pathways that may help explain the molecular mechanics of vitamin A deficiency. We localised BMP4 gene expression to adult germ cells, in particular spermatogonia, at both the mRNA and protein level. We generated VAD mice and found that in the absence of retinoids in vivo, bmp4 gene expression was significantly upregulated in the testis. We also observed that the expression of bmp4 is downregulated by retinoid treatment in germ cells isolated from vitamin A sufficient mice. Expression of bmp4 mRNA in isolated spermatogonia was more sensitive to ROL rather than RA. Our results may reflect a direct requirement for ROL by germ cells for the resumption of spermatogenesis in VAD animals that involves the regulation of BMP4 expression. Furthermore our observations suggest that retinoid signalling in germ cells is different to that observed in somatic cells, and may provide insights into the role of retinoids in spermatogenesis.

scholarly journals Loss of histone methyltransferase ASH1L in the developing mouse brain causes autistic-like behaviors

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Yuen Gao ◽  
Natalia Duque-Wilckens ◽  
Mohammad B. Aljazi ◽  
Yan Wu ◽  
Adam J. Moeser ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mouse Brain ◽  
Molecular Mechanisms ◽  
Gene Mutations ◽  
Autism Spectrum ◽  
Normal Brain ◽  
Critical Function ◽  
Developmental Defects ◽  
Neurodevelopmental Disease ◽  
Developing Mouse Brain

AbstractAutism spectrum disorder (ASD) is a neurodevelopmental disease associated with various gene mutations. Recent genetic and clinical studies report that mutations of the epigenetic gene ASH1L are highly associated with human ASD and intellectual disability (ID). However, the causality and underlying molecular mechanisms linking ASH1L mutations to genesis of ASD/ID remain undetermined. Here we show loss of ASH1L in the developing mouse brain is sufficient to cause multiple developmental defects, core autistic-like behaviors, and impaired cognitive memory. Gene expression analyses uncover critical roles of ASH1L in regulating gene expression during neural cell development. Thus, our study establishes an ASD/ID mouse model revealing the critical function of an epigenetic factor ASH1L in normal brain development, a causality between Ash1L mutations and ASD/ID-like behaviors in mice, and potential molecular mechanisms linking Ash1L mutations to brain functional abnormalities.

scholarly journals Mediterranean Diet Reduces Monocyte Inflammatory Gene Expression and Influences Social Behavior in Nonhuman Primates

2020 ◽  
Author(s):  
Corbin S.C. Johnson ◽  
Carol A. Shively ◽  
Kristofer T. Michalson ◽  
Amanda J. Lea ◽  
Ryne J. DeBo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mediterranean Diet ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Western Diet ◽  
Primate Model ◽  
Inflammatory Gene Expression ◽  
Inflammatory Gene ◽  
Increased Risk ◽  
Diet Manipulation

AbstractWestern diet consumption is associated with inflammation, cardiometabolic disease, and mortality in humans, while Mediterranean diet consumption confers protective effects. One likely pathway for this association is through environmentally induced changes in monocyte function, yet the underlying mechanisms remain elusive. We conducted the first randomized, long-term diet manipulation in a non-human primate model to determine whether Western- or Mediterranean-like diets alter monocyte polarization and health. Monocyte gene expression profiles differed markedly between the two diet groups, with significant differences in over 40% of expressed genes. The Western diet induced a more proinflammatory monocyte phenotype overall and upregulated specific monocyte polarization genes. Diet also disrupted the coexpression of numerous gene pairs, including small RNAs and transcription factors associated with metabolism and adiposity in humans. Diet altered affiliative and anxiety-associated behaviors and mediation analysis showed that the diet-altered behaviors contributed significantly (∼50% of the effect of diet on gene expression) to 25% of the differentially expressed genes, suggesting that diet effects on central mechanisms also modulate monocyte gene expression. Together, these results identify both behavioral and molecular mechanisms underlying the health benefits of a Mediterranean diet regimen.Significance StatementSome of our largest public health burdens are driven by dietary changes associated with industrialization, but we still know very little about the molecular mechanisms underlying this link. Characteristic “Western diets” have been associated with increased risk for diseases related to chronic inflammation, while Mediterranean diets have anti-inflammatory benefits. Here, we identify causal effects of diet on inflammatory gene expression where consumption of the Mediterranean diet reduced inflammatory gene expression in monocytes. Additionally, our diet manipulation induced behavioral changes associated with anxiety and social integration, where Mediterranean-fed animals exhibited more positive affiliative behaviors and reduced anxiety. These behaviors were associated with 25% of the diet-affected genes, suggesting an important behavioral route through which diet can impact immune function.

New Issues in Developing Effective Approaches for the Prevention and Control of Vitamin A Deficiency

1998 ◽  
Vol 19 (2) ◽  
pp. 137-148 ◽  
Author(s):  
Martin W. Bloem ◽  
Saskia de Pee ◽  
Ian Darnton-Hill
Keyword(s):  
At Risk ◽  
Vitamin A ◽  
Prevention And Control ◽  
Control Strategies ◽  
Vitamin A Deficiency ◽  
Life Cycle Approach ◽  
Mortality And Morbidity ◽  
Increased Risk ◽  
To Come ◽  
And Control

Even mild to moderate vitamin A deficiency is now recognized as an important factor in child health and survival. This has given increased emphasis to the goal of virtually eliminating vitamin A deficiency and its consequences, including blindness, by the end of the decade. The implications of vitamin A deficiency, however, vary according to the group at risk, and this needs to be addressed when looking at ways to achieve the goal. In pre-school children, vitamin A deficiency can lead to increased risk of mortality and morbidity and to blindness. In pregnant and lactating women, it can lead to night-blindness and appears to have implications for maternal morbidity and mortality. Although the immediate health consequences for schoolchildren and adolescents are not completely known, they are probably less dramatic. Nevertheless, it is clear that there is a cross-generational cycle leading to and perpetuating vitamin A deficiency in affected communities. This also has implications when addressing prevention and control strategies. The existing, somewhat successful approach has been to target children aged six months to six years; it is implicit that this criterion is used to measure progress towards the end-of-decade goals. A broader, complementary, life-cycle approach to vitamin A deficiency is now appropriate in many countries. There is increasing emphasis on such approaches, i.e., fortifying foods with vitamin A and improving the diet, which address the whole population at risk. A mix of interventions will give governments the chance to shift from a subsidized vitamin A capsule programme to more sustainable, non-subsidized, consumer-funded vitamin A interventions, although in an appreciable number of countries, supplementation with vitamin A will be a necessity for some years to come. Guidelines to assist governments in such transitions are a high priority.

Moderate maternal vitamin A deficiency alters myogenic regulatory protein expression and perinatal organ growth in the rat

2005 ◽  
Vol 288 (1) ◽  
pp. R73-R79 ◽  
Author(s):  
D. Downie ◽  
C. Antipatis ◽  
M. I. Delday ◽  
C. A. Maltin ◽  
A. A. Sneddon
Keyword(s):  
Vitamin A ◽  
Muscle Development ◽  
Vitamin A Deficiency ◽  
Regulatory Protein ◽  
Female Rats ◽  
Health Concern ◽  
Myogenic Regulatory Factor ◽  
Mortality And Morbidity ◽  
Regulatory Pathways ◽  
Increased Risk

Vitamin A deficiency is one of the most common dietary deficiencies in the developing world and is a major health concern where it is associated with increased risk of fetal and infant mortality and morbidity. Early studies in the rat demonstrated that, in addition to respiratory problems, neonates showed evidence of mobility problems in response to moderate vitamin A deficiency. This study investigated whether moderate deficiency of this vitamin plays a role in regulating key skeletal muscle regulatory pathways during development. Thirty female rats were fed vitamin A-moderate (VAM) or vitamin A-sufficient diets from weaning and throughout pregnancy. Fetal and neonatal hindlimb and muscle samples were collected on days 13.5, 15.5, 17.5, and 19.5 of pregnancy and 1 day following birth. Mothers fed the VAM diet had reduced retinol concentrations at all time points studied ( P < 0.01), and neonates had reduced relative lung weights ( P < 0.01). Fetal weight and survival did not differ between groups but neonatal survival was lower in the VAM group where neonates had increased relative heart weights ( P < 0.05). Analysis of myogenic regulatory factor expression and calcineurin signaling in fetuses and neonates demonstrated decreased protein levels of myf5 [50% at 17.5 dg ( P < 0.05)], myogenin [70% at birth ( P < 0.001)], and myosin heavy chain fast [50% at birth ( P < 0.05)] in response to moderate vitamin A deficiency. Overall, these changes suggest that vitamin A status during pregnancy may have important implications for fetal muscle development and subsequent muscle function in the offspring.

scholarly journals The Epidemiology of Global Micronutrient Deficiencies

2015 ◽  
Vol 66 (Suppl. 2) ◽  
pp. 22-33 ◽  
Author(s):  
Regan L. Bailey ◽  
Keith P. West Jr. ◽  
Robert E. Black
Keyword(s):  
Vitamin A ◽  
Immune Function ◽  
Vitamin A Deficiency ◽  
Macrocytic Anemia ◽  
Microcytic Anemia ◽  
Endocrine Function ◽  
Micronutrient Deficiencies ◽  
Perinatal Complications ◽  
Poor Growth ◽  
Increased Risk

Micronutrients are essential to sustain life and for optimal physiological function. Widespread global micronutrient deficiencies (MNDs) exist, with pregnant women and their children under 5 years at the highest risk. Iron, iodine, folate, vitamin A, and zinc deficiencies are the most widespread MNDs, and all these MNDs are common contributors to poor growth, intellectual impairments, perinatal complications, and increased risk of morbidity and mortality. Iron deficiency is the most common MND worldwide and leads to microcytic anemia, decreased capacity for work, as well as impaired immune and endocrine function. Iodine deficiency disorder is also widespread and results in goiter, mental retardation, or reduced cognitive function. Adequate zinc is necessary for optimal immune function, and deficiency is associated with an increased incidence of diarrhea and acute respiratory infections, major causes of death in those <5 years of age. Folic acid taken in early pregnancy can prevent neural tube defects. Folate is essential for DNA synthesis and repair, and deficiency results in macrocytic anemia. Vitamin A deficiency is the leading cause of blindness worldwide and also impairs immune function and cell differentiation. Single MNDs rarely occur alone; often, multiple MNDs coexist. The long-term consequences of MNDs are not only seen at the individual level but also have deleterious impacts on the economic development and human capital at the country level. Perhaps of greatest concern is the cycle of MNDs that persists over generations and the intergenerational consequences of MNDs that we are only beginning to understand. Prevention of MNDs is critical and traditionally has been accomplished through supplementation, fortification, and food-based approaches including diversification. It is widely accepted that intervention in the first 1,000 days is critical to break the cycle of malnutrition; however, a coordinated, sustainable commitment to scaling up nutrition at the global level is still needed. Understanding the epidemiology of MNDs is critical to understand what intervention strategies will work best under different conditions.

scholarly journals Increased Risk of High Body Fat and Altered Lipid Metabolism Associated to Suboptimal Consumption of Vitamin A Is Modulated by Genetic Variants rs5888 (SCARB1), rs1800629 (UCP1) and rs659366 (UCP2)

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2588
Author(s):  
Sebastià Galmés ◽  
Andreu Palou ◽  
Francisca Serra
Keyword(s):  
Gene Expression ◽  
Lipid Metabolism ◽  
Vitamin A ◽  
Body Fat ◽  
Genetic Variants ◽  
Mononuclear Cells ◽  
Metabolic Response ◽  
Ex Vivo ◽  
P Value ◽  
Increased Risk

Obesity is characterized by an excessive body fat percentage (BF%). Animal and cell studies have shown benefits of vitamin A (VA) on BF% and lipid metabolism, but it is still controversial in humans. Furthermore, although some genetic variants may explain heterogeneity in VA plasma levels, their role in VA metabolic response is still scarcely characterized. This study was designed as a combination of an observational study involving 158 male subjects followed by a study with a well-balanced genotype–phenotype protocol, including in the design an ex vivo intervention study performed on isolated peripheral blood mononuclear cells (PBMCs) of the 41 former males. This is a strategy to accurately identify the delivery of Precision Nutrition recommendations to targeted subjects. The study assesses the influence of rs5888 (SCARB1), rs659366 (UCP2), and rs1800629 (UCP1) variants on higher BF% associated with suboptimal VA consumption and underlines the cellular mechanisms involved by analyzing basal and retinoic acid (RA) response on PBMC gene expression. Data show that male carriers with the major allele combinations and following suboptimal-VA diet show higher BF% (adjusted ANOVA test p-value = 0.006). Genotype–BF% interaction is observed on oxidative/inflammatory gene expression and also influences lipid related gene expression in response to RA. Data indicate that under suboptimal consumption of VA, carriers of VA responsive variants and with high-BF% show a gene expression profile consistent with an impaired basal metabolic state. The results show the relevance of consuming VA within the required amounts, its impact on metabolism and energy balance, and consequently, on men’s adiposity with a clear influence of genetic variants SCARB1, UCP2 and UCP1.

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