Genetic variants in selenoprotein genes modulate biomarkers of selenium status in response to Brazil nut supplementation (the SU.BRA.NUT study)

This work was supported by Brazilian grants from São Paulo Research Foundation to JLSD (Fundação de Amparo à Pesquisa do Estado de São Paulo-FAPESP processes: 2011/17720-0 and 2015/10146-8). Funding source had no involvement in study design, collection, analysis and interpretation of data from the present research.Peer reviewedPostprin

Effets de la matrice alimentaire sur la biodisponibilité des micronutriments et phytomicronutriments lipidiques

International audienceIn order for ingested lipid micronutrients and phytochemicals (vitamin A, D, E. K. carotenoids, phytosterols, some potyphenots...) to exert their biological/health effects, they must usually reach systemic circulation. The absorption process of these molecules includes several steps (extraction from the food matrix, incorporation into mixed micelles, uptake by enterocytes...) whose efficiencies are strongly influenced by the characteristics of the matrix of the food source or co-ingested foods. Carotenoid release from their matrix is lower when they are incorporated in chloroplasts (green leafy vegetables) compared to chromoplasts (yellow, orange and red vegetables and fruits) and animal products. Other constituents from the meal can increase (triglycerides) or decrease (fibres, phytosterols, other microconstituents) their bioavailability while some technological/cooking modifications can lead to an increase in the absorption efficiency. These factors can also modify the kinetics of appearance of these molecules in the systemic circulation but the biological consequences thereof are not known. Abetter knowledge of the effect of food matrices on the bioavailability of these compounds would allow nutritionists to propose actions for the food industry or individuals in order to limit deficiencies and increase their health benefits. Taking into account this factor would also allow scientists to better analyse their effects in nutritional epidemiology studies

Effets de régimes hyperlipidique et cafeteria sur le développement de l'obésité et ses désordres associés chez la souris

Introduction: Obesity results from a prolonged imbalance between energy intake and energy expenditure, as depending on basal metabolic rate, heat production, thermogenic effects of the diet and physical activity. Diet-induced obesity (DIO) in rodents can be achieved by different regimens and approaches. Diets providing a high fat intake have been established as a "gold standard" to generate obese rodent models and have proven to initiate pathologies similar to those encountered in humans. However, this dietary treatment is far from being standardized and its relevance has been criticised on the basis of findings in humans that total energy intake rather than fat per se determines body fat accumulation in humans. Hence, cafeteria diets have been introduced by providing a choice of several palatable food items of variable composition, appearance and texture in addition to a non-purified diet. Those approaches have been shown to induce obesity by a hyperphagia. Objective: This thesis aimed at comparing the effects of a high fat vs. a cafeteria diet on food intake, weight gain and determinants of energy homeostasis and metabolism in obese mice. Results: Our key findings demonstrate that both a high fat and a cafeteria diet were almost equally efficient in driving an obese phenotype but did not necessarily elicit the same metabolic changes. The cafeteria diet as characterised by a higher carbohydrate (mainly sucrose) and lower fat content seemed to be more deleterious for liver steatohepatosis and provoked more pronounced changes in the gut microbiota. Despite a lower cholesterol content than in the high fat diet, mice fed the cafeteria diet presented levels of circulating cholesterol as high as animals on a high fat diet. Changes in gene expression in liver and intestine suggested an increased de novo synthesis of cholesterol and altered transport and those effects were more pronounced in animals receiving a high fat diet. Most strikingly, the pronounced effects of the two high calorie diets causing obesity when compared to animals on control diet remaining lean vanished when diets with identical composition were supplied in powder form and not as standard pellets. Here, even the control diet with a high starch but very low fat content caused a substantial weight gain with only minor differences to the two other high-calorie diets. Conclusion: The results presented here raise the question of whether high fat diets used for induction of obesity are the proper models to simulate human obesity and its pathologies. Cafeteria diets are equally effective and are closer to human diets.Introduction : L'obésité est causée par un déséquilibre prolongé entre les apports énergétiques et l'activité physique, dépendant du métabolisme de base, de la production de chaleur et des effets thermogéniques du régime et de l'activité physique. Chez les rongeurs, l'obésité induite par le régime peut être obtenue par différents régimes et approches. A cet égard, les régimes hyperlipidiques sont considérés comme les régimes de référence pour générer des modèles de l'obésité chez le rongeur et engendrent des pathologies similaires à celles rencontrées chez l'homme. Cependant, ce régime alimentaire est loin d'être standardisé et a été critiqué sur le fait que la prise énergétique totale et non uniquement les lipides régissait l'accumulation de graisse corporelle chez l'homme. Ainsi, les régimes cafétéria ont été introduits : en offrant en plus d'un régime non purifié un choix de plusieurs aliments appétants, de composition, d'apparence et de texture différentes, ils permettent le développement de l'obésité en déclenchant l'hyperphagie. Objectif : L'objet de ces travaux a été de comparer chez des souris obèses les effets d'un régime hyperlipidique à ceux d'un régime cafétéria sur la prise de nourriture, la prise de poids et les déterminants du métabolisme et de l'homéostase énergétique. Résultats : Nos résultats démontrent qu'un régime hyperlipidique et un régime cafeteria permettent tous deux d'obtenir un phénotype obèse mais sans causer nécessairement les mêmes changements métaboliques. Le régime cafétéria, caractérisé par un contenu en glucides (principalement le sucrose) plus élevé et un contenu en lipides plus faible, semble avoir des conséquences plus néfastes pour le foie et provoque des changements plus prononcés au niveau du microbiote intestinal. Malgré un contenu en cholestérol plus faible que dans le régime hyperlipidique, les souris nourries au régime cafétéria présentaient une cholestérolémie similaire. Les niveaux d'expression des gènes impliqués dans le métabolisme du cholestérol dans l'intestin grêle et le foie suggèrent une augmentation de la synthèse de cholestérol de novo et une modification de son transport, ces effets étant plus marqués chez les souris nourries au régime hyperlipidique. Conclusion : Ces résultats remettent en question le statut des régimes hyperlipidiques pour déclencher l'obésité et pour générer ses pathologies associées. Les régimes cafétéria sont aussi efficaces à cet égard et sont plus proches des régimes consommés chez l'homme

Bioavailability of Fat-Soluble Vitamins and Phytochemicals in Humans: Effects of Genetic Variation

“preprint posted with permission from the Annual Review of Nutrition,2019, 38, © by Annual Reviews, http://www.annualreviews.org.”International audienceRecent data have shown that the interindividual variability in the bioavailability of vitamin A (beta-carotene), D, E, carotenoids (lutein and lycopene), as well as that of phytosterols is modulated by single nucleotide polymorphisms (SNPs). The identified SNPs are in or near genes involved in intestinal uptake/efflux of these compounds, as well as in genes involved in their metabolism and transport. The phenotypic effect of each SNP is usually low but combinations of SNPs can explain a significant part of the variability. Nevertheless, existing results should be considered as preliminary since they have not been validated in other cohorts yet. Guidelines for future studies are provided in order to obtain sound associations that could be used to build consolidated genetic scores that could allow the proposition of tailored dietary allowances, i.e.taking into account the multi-loci genotypic signature of groups of different ethnic originor even of individuals

Overview of carotenoid bioavailability determinants: From dietary factors to host genetic variations: Carotenoid bioavailability determinants

International audienceCarotenoids are C-30 or C-40 based pigments with antioxidant/anti-inflammatory properties, some possessing vitamin A activity. Their dietary intake, especially within fruits and vegetables, has been associated with a decreased risk of chronic diseases, including type-2 diabetes, cardiovascular diseases, age-related macular degeneration, and several types of cancer. However, their bioavailability is wide ranging and is affected by numerous factors. Recent findings showing that the intestinal absorption of carotenoids involves proteins have raised new relevant questions about factors that can affect their bioavailability. It is therefore opportune to present a current overview of this topic.Scope and approach: This review begins by exploring what is known, as well as what is unknown, about the metabolism of carotenoids in the human upper gastrointestinal tract and then presents a methodical evaluation of factors assumed to affect carotenoid bioavailability.Key findings and conclusions : Numerous unanswered questions remain about the metabolism of carotenoids in the intestinal lumen and about the factors affecting their absorption efficiency. These gaps need to be filled to be able to better understand individual, variable responses to these compounds so as to promote guidelines towards personalized dietary recommendation in order to increase carotenoid absorption efficiency and hence their health effects. Two main conclusions can be drawn. First, the efficiency of carotenoid absorption is affected by several dietary factors (e.g. food matrix, fat, and fat-soluble micronutrients). Second, carotenoid bioavailability also depends on host-related factors, e.g. diseases, life-style habits, gender and age, as well as genetic variations including single nucleotide polymorphisms

Effets de régimes hyperlipidique et cafeteria sur le développement de l'obésité et ses désordres associés chez la souris

Introduction : L'obésité est causée par un déséquilibre prolongé entre les apports énergétiques et l'activité physique, dépendant du métabolisme de base, de la production de chaleur et des effets thermogéniques du régime et de l'activité physique. Chez les rongeurs, l'obésité induite par le régime peut être obtenue par différents régimes et approches. A cet égard, les régimes hyperlipidiques sont considérés comme les régimes de référence pour générer des modèles de l'obésité chez le rongeur et engendrent des pathologies similaires à celles rencontrées chez l'homme. Cependant, ce re gime alimentaire est loin d'être standardisé et a été critiqué sur le fait que la prise énergétique totale et non uniquement les lipides régissait l'accumulation de graisse corporelle chez l'homme. Ainsi, les régimes cafétéria ont été introduits : en offrant en plus d'un régime non purifié un choix de plusieurs aliments appétants, de composition, d'apparence et de texture différentes, ils permettent le développement de l'obésité en déclenchant l'hyperphagie. Objectif : L'objet de ces travaux a été de comparer chez des souris obèses les effets d'un régime hyperlipidique à ceux d'un régime cafétéria sur la prise de nourriture, la prise de poids et les déterminants du métabolisme et de l'homéostase énergétique. Résultats : Nos résultats démontrent qu'un régime hyperlipidique et un régime cafeteria permettent tous deux d'obtenir un phénotype obèse mais sans causer nécessairement les mêmes changements métaboliques. Le régime cafétéria, caractérisé par un contenu en glucides (principalement le sucrose) plus élevé et un contenu en lipides plus faible, semble avoir des conséquences plus néfastes pour le foie et provoque des changements plus prononcés au niveau du microbiote intestinal. Malgré un contenu en cholestérol plus faible que dans le régime hyperlipidique, les souris nourries au régime cafétéria présentaient une cholestérolémie similaire. Les niveaux d'expression des gènes impliqués dans le métabolisme du cholestérol dans l'intestin grêle et le foie suggèrent une augmentation de la synthèse de cholestérol de novo et une modification de son transport, ces effets étant plus marqués chez les souris nourries au régime hyperlipidique. Conclusion : Ces résultats remettent en question le statut des régimes hyperlipidiques pour déclencher l'obésité et pour générer ses pathologies associées. Les régimes cafétéria sont aussi efficaces à cet égard et sont plus proches des régimes consommés chez l'homme.Introduction: Obesity results from a prolonged imbalance between energy intake and energy expenditure, as depending on basal metabolic rate, heat production, thermogenic effects of the diet and physical activity. Diet-induced obesity (DIO) in rodents can be achieved by different regimens and approaches. Diets providing a high fat intake have been established as a "gold standard" to generate obese rodent models and have proven to initiate pathologies similar to those encountered in humans. However, this dietary treatment is far from being standardized and its relevance has been criticised on the basis of findings in humans that total energy intake rather than fat per se determines body fat accumulation in humans. Hence, cafeteria diets have been introduced by providing a choice of several palatable food items of variable composition, appearance and texture in addition to a non-purified diet. Those approaches have been shown to induce obesity by a hyperphagia. Objective: This thesis aimed at comparing the effects of a high fat vs. a cafeteria diet on food intake, weight gain and determinants of energy homeostasis and metabolism in obese mice. Results: Our key findings demonstrate that both a high fat and a cafeteria diet were almost equally efficient in driving an obese phenotype but did not necessarily elicit the same metabolic changes. The cafeteria diet as characterised by a higher carbohydrate (mainly sucrose) and lower fat content seemed to be more deleterious for liver steatohepatosis and provoked more pronounced changes in the gut microbiota. Despite a lower cholesterol content than in the high fat diet, mice fed the cafeteria diet presented levels of circulating cholesterol as high as animals on a high fat diet. Changes in gene expression in liver and intestine suggested an increased de novo synthesis of cholesterol and altered transport and those effects were more pronounced in animals receiving a high fat diet. Most strikingly, the pronounced effects of the two high calorie diets causing obesity when compared to animals on control diet remaining lean vanished when diets with identical composition were supplied in powder form and not as standard pellets. Here, even the control diet with a high starch but very low fat content caused a substantial weight gain with only minor differences to the two other high-calorie diets. Conclusion: The results presented here raise the question of whether high fat diets used for induction of obesity are the proper models to simulate human obesity and its pathologies. Cafeteria diets are equally effective and are closer to human diets.PARIS-AgroParisTech Centre Paris (751052302) / SudocSudocFranceF

Genetic Variations Associated with Vitamin A Status and Vitamin A Bioavailability

Blood concentration of vitamin A (VA), which is present as different molecules, i.e., mainly retinol and provitamin A carotenoids, plus retinyl esters in the postprandial period after a VA-containing meal, is affected by numerous factors: dietary VA intake, VA absorption efficiency, efficiency of provitamin A carotenoid conversion to VA, VA tissue uptake, etc. Most of these factors are in turn modulated by genetic variations in genes encoding proteins involved in VA metabolism. Genome-wide association studies (GWAS) and candidate gene association studies have identified single nucleotide polymorphisms (SNPs) associated with blood concentrations of retinol and β-carotene, as well as with β-carotene bioavailability. These genetic variations likely explain, at least in part, interindividual variability in VA status and in VA bioavailability. However, much work remains to be done to identify all of the SNPs involved in VA status and bioavailability and to assess the possible involvement of other kinds of genetic variations, e.g., copy number variants and insertions/deletions, in these phenotypes. Yet, the potential usefulness of this area of research is exciting regarding the proposition of more personalized dietary recommendations in VA, particularly in populations at risk of VA deficiency

Genetic Variations Involved in Vitamin E Status

Vitamin E (VE) is the generic term for four tocopherols and four tocotrienols that exhibit the biological activity of α-tocopherol. VE status, which is usually estimated by measuring fasting blood VE concentration, is affected by numerous factors, such as dietary VE intake, VE absorption efficiency, and VE catabolism. Several of these factors are in turn modulated by genetic variations in genes encoding proteins involved in these factors. To identify these genetic variations, two strategies have been used: genome-wide association studies and candidate gene association studies. Each of these strategies has its advantages and its drawbacks, nevertheless they have allowed us to identify a list of single nucleotide polymorphisms associated with fasting blood VE concentration and α-tocopherol bioavailability. However, much work remains to be done to identify, and to replicate in different populations, all the single nucleotide polymorphisms involved, to assess the possible involvement of other kind of genetic variations, e.g., copy number variants and epigenetic modifications, in order to establish a reliable list of genetic variations that will allow us to predict the VE status of an individual by knowing their genotype in these genetic variations. Yet, the potential usefulness of this area of research is exciting with regard to personalized nutrition and for future clinical trials dedicated to assessing the biological effects of the various isoforms of VE

Bioavailability of vitamin E in humans: an update

International audienceVitamin E is essential for human health and may play a role in the prevention of some degenerative diseases. Its bioavailability, however, is wide ranging and is affected by numerous factors. Recent findings showing that the intestinal absorption of vitamin E involves proteins have raised new relevant questions about factors that can affect bioavailability. It is, therefore, opportune to present a current overview of this topic. This review begins by exploring what is known, aswell as what is unknown, about the metabolization of vitamin E in the human upper gastrointestinal tract and then presents a methodical evaluation of factors assumed to affect vitamin E bioavailability. Three main conclusions can be drawn. First, the proteins ABCA1, NPC1L1, and SR-BI are implicated in the absorption of vitamin E. Second, the efficiency of vitamin E absorption is widely variable, though not accurately known (i.e., between 10% and 79%), and is affected by several dietary factors (e.g., food matrix, fat, and fat-soluble micronutrients). Finally, numerous unanswered questions remain about the metabolization of vitamin E in the intestinal lumen and about the factors affecting the efficiency of vitamin E absorption