Alpha‐tocopherol transport in the lung is affected by the apoE genotype—Studies in transgenic apoE3 and apoE4 mice

Huebbe, Patricia; Jofre-Monseny, Laia; Rimbach, Gerald

doi:10.1002/iub.177

Cited by 22 publications

(17 citation statements)

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“…Interestingly, APOE4 carriers seem to be less prone to vitamin D-deficiency, as extrapolated from population-wide APOE4 geographical distributions (37). However, animal studies using APOE4 transgenic mice have found significantly lower alpha-tocopherol levels in the lung compared to APOE3 controls (38). …”

Section: Discussionmentioning

confidence: 99%

Apolipoprotein E4 influences growth and cognitive responses to micronutrient supplementation in shantytown children from northeast Brazil

Mitter¹,

Oriá²,

Kvalsund³

et al. 2012

Clinics

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OBJECTIVE:Apolipoprotein E4 may benefit children during early periods of life when the body is challenged by infection and nutritional decline. We examined whether apolipoprotein E4 affects intestinal barrier function, thereby improving short-term growth and long-term cognitive outcomes in Brazilian shantytown children.METHODS:A total of 213 Brazilian shantytown children with below-median height-for-age z-scores (HAZ) received 200,000 IU of retinol (every four months), zinc (40 mg twice weekly), or both for one year, with half of each group receiving glutamine supplementation for 10 days. Height-for-age z-scores, weight-for-age z-scores, weight-for-height z-scores, and lactulose:mannitol ratios were assessed during the initial four months of treatment. An average of four years (range 1.4-6.6) later, the children underwent cognitive testing to evaluate non-verbal intelligence, coding, verbal fluency, verbal learning, and delayed verbal learning. Apolipoprotein E4 carriage was determined by PCR analysis for 144 children.RESULTS:Thirty-seven children were apolipoprotein E4(+), with an allele frequency of 13.9%. Significant associations were found for vitamin A and glutamine with intestinal barrier function. Apolipoprotein E4(+) children receiving glutamine presented significant positive Pearson correlations between the change in height-for-age z-scores over four months and delayed verbal learning, along with correlated changes over the same period in weight-for-age z-scores and weight-for-height z-scores associated with non-verbal intelligence quotients. There was a significant correlation between vitamin A supplementation of apolipoprotein E4(+) children and improved delta lactulose/mannitol. Apolipoprotein E4(-) children, regardless of intervention, exhibited negative Pearson correlations between the change in lactulose-to-mannitol ratio over four months and verbal learning and non-verbal intelligence.CONCLUSIONS:During development, apolipoprotein E4 may function concomitantly with gut-tropic nutrients to benefit immediate nutritional status, which can translate into better long-term cognitive outcomes.

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Section: Discussionmentioning

confidence: 99%

Apolipoprotein E4 influences growth and cognitive responses to micronutrient supplementation in shantytown children from northeast Brazil

Mitter¹,

Oriá²,

Kvalsund³

et al. 2012

Clinics

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“…vitamin E concentration is lower in apoE4-than apoE3-targeted replacement mice, which is most likely due to the lower expression of LDL-receptor and related receptor classes mediating vitamin E uptake (103) . Furthermore, degradation of vitamin E may be increased in the apoE e4 genotype contributing to lower tissue retention and therefore possibly lower vitamin E status in peripheral tissues (104) .…”

Section: Proceedings Of the Nutrition Societymentioning

confidence: 98%

ApoE genotype: from geographic distribution to function and responsiveness to dietary factors

2012

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ApoE is a key protein in lipid metabolism with three major isoforms. ApoE allele frequencies show non-random global distribution especially in Europe with high apoE e3 frequency in the Mediterranean area, whereas the apoE e4 genotype is enriched in Northern Europe. The apoE e4 genotype is one of the most important genetic risk factors for age-dependent chronic diseases, including CVD and Alzheimer's disease (AD). The apoE polymorphism has been shown to impact on blood lipids, biomarkers of oxidative stress and chronic inflammation, which all may contribute to the isoform-dependent disease risk. Studies in mice and human subjects indicate that the apoE e3 but not the apoE e4 genotype may significantly benefit from dietary flavonoids (e.g. quercetin) and n-3 fatty acids. Metabolism of lipid soluble vitamins E and D is likewise differentially affected by the apoE genotype. Epidemiological and experimental evidence suggest a better vitamin D status in apoE e4 than e3 subjects indicating a certain advantage of e4 over e3. The present review aims at evaluation of current data available on interactions between apoE polymorphism and dietary responsiveness to flavonoids, fat soluble vitamins and n-3 fatty acids. Likewise, distinct geographic distribution and chronic disease risk of the different apoE isoforms are addressed.

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“…It is also reported that human plasma levels of a-tocopherol but not g-tocopherol are increased in male adults and children by the apolipoprotein A5 1131T.C gene polymorphism (15,16). In mice, apoE4 mice have lower plasma a-tocopherol than apoE3 mice (17).…”

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confidence: 99%

Two Faces of Vitamin E in the Lung

Cook‐Mills

Abdala-Valencia

Hartert

2013

Am J Respir Crit Care Med

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Asthma and allergic lung disease occur as complex environmental and genetic interactions. Clinical studies of asthma indicate a number of protective dietary factors, such as vitamin E, on asthma risk. However, these studies have had seemingly conflicting outcomes. In this perspective, we discuss opposing regulatory effects of tocopherol isoforms of vitamin E, mechanisms for tocopherol isoform regulation of allergic lung inflammation, association of vitamin E isoforms with outcomes in clinical studies, and how the variation in global prevalence of asthma may be explained, at least in part, by vitamin E isoforms.Keywords: asthma; a-tocopherol; g-tocopherol; human; mouse Asthma and allergic lung disease occur as complex environmental and genetic interactions (1). The World Health Organization has reported that the prevalence of asthma from 1950 to the present has increased in many countries, including countries with high rates of asthma, intermediate rates of asthma, or low rates of asthma (2-4). The marked differences in rates of asthma within countries, in migrating populations, and over relatively short periods of time support an important role of the local environment, such as diet, in asthma inception. Prospective epidemiological studies, observational cross-sectional studies, and some randomized prevention trials have demonstrated the impact of a number of protective dietary factors, such as vitamin E, on asthma risk. However, these studies have had seemingly conflicting outcomes. We need to determine why there are low rates of allergic disease in developing countries and better understand the differences in diet and lifestyle that may really underpin allergic disease. One environmental change over the past 40 years has been an increase in the g-tocopherol isoform of vitamin E in the diet and in infant formulas (5, 6). We recently demonstrated that g-tocopherol increases allergic lung inflammation in mice (6)(7)(8). In this perspective, we discuss why we have yet to uncover the complex and potentially protective effects of isoforms of vitamin E on asthma in humans and in animal models of lung inflammation. We also review mechanisms for tocopherol isoform regulation of allergic lung inflammation in animals and discuss how the variation in global prevalence of asthma may be explained, at least in part, by country-specific plasma g-tocopherol differences.Vitamin E consists of natural isoforms and synthetic racemic isoforms. The eight natural isomers are d-a-, d-b-, d-g-, d-d-tocopherol and d-a-, d-b-, d-g-, d-d-tocotrienol. Plants synthesize the natural isoforms from tyrosine and chlorophyll (9). Then, these tocols are consumed in the diet from plant lipids. Mammals do not interconvert the tocopherol isoforms. The most abundant isoforms are a-tocopherol and g-tocopherol, which differ by one methyl group ( Figure 1A). There are approximately 10-fold higher tissue concentrations of a-tocopherol than g-tocopherol due to preferential transfer of a-tocopherol in the liver by a-tocopherol transfer protein and due to ...

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Alpha‐tocopherol transport in the lung is affected by the apoE genotype—Studies in transgenic apoE3 and apoE4 mice

Cited by 22 publications

References 17 publications

Apolipoprotein E4 influences growth and cognitive responses to micronutrient supplementation in shantytown children from northeast Brazil

Apolipoprotein E4 influences growth and cognitive responses to micronutrient supplementation in shantytown children from northeast Brazil

ApoE genotype: from geographic distribution to function and responsiveness to dietary factors

Two Faces of Vitamin E in the Lung

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