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Background: University students have low levels of physical activity and high levels of sedentary behaviors that were exacerbated by the COVID-19 pandemic. Even before the pandemic, there was poor uptake of university sports activities. Therefore, it is essential to develop and test innovative programs to increase students’ motivation to engage in physical activity in order to prevent any future deterioration in their general health. Objective: This exploratory study was conducted to test the effectiveness of a physical activity program that was co-constructed with students. Methods: First, a workshop drawing on social design methodologies and the fundamentals of physical activity programs was conducted to assess students’ needs and desires in terms of physical activity. Second, the effectiveness of a program co-constructed with students on the basis of this workshop was assessed on physical and mental health parameters. The results showed that the workshop outcomes allowed the physical activity program to be tailored to meet students’ expectations (e.g., session duration and type of activities). This innovative physical activity program was found to improve body image, autonomous motivation, and certain physical parameters. At the end of the 8-week program, the adherence rate was 89%, and 83% of the final respondents expressed a wish to re-enroll for the following semester. Conclusions: Involving students and considering their wishes, needs, and objectives could facilitate the development of attractive and innovative programs.

International audience; Background and Aim: Childhood obesity is associated with vitamin D (VD) deficiency and vascular dysfunction. Considering evidence indicates that VD may improve vascular function, this study, for the first time, assessed the effect of VD supplementation on microvascular reactivity in obese adolescents (OA).Methods and Results: This randomized controlled trial included 26 OA, receiving fruit juice with (n=13) or without VD (4000 IU/d; n=13) over a 3-month lifestyle program, as well as 23 normal-weight adolescents (controls). The primary outcome was the pre-to-post-program change in microvascular reactivity determined by laser speckle contrast imaging with acetylcholine and sodium nitroprusside iontophoresis. Changes in 25 hydroxyvitamin D (25(OH)D), flow-mediated dilation (FMD), nitrate-mediated dilation (NMD), insulin resistance (HOMA-IR) and inflammatory markers (C-reactive protein [CRP]) were monitored. At inclusion, in comparison to controls, OA exhibited lower total and free 25(OH)D, impaired microvascular responses, and impaired FMD, but similar NMD. After the lifestyle program, total and free 25(OH)D increased in all OA, with a greater increase in those receiving VD supplements. HOMA-IR and CRP decreased in all OA. Neither FMD nor NMD were altered in either group. Endothelium-dependent microvascular reactivity only increased in the VD-supplemented group, reaching values comparable to that of controls. Similar results were found when analyzing only OA with a VD deficiency at baseline.Conclusion: VD supplementation during a lifestyle program attenuated microvascular dysfunction in OA without altering macrovascular function.Registration number for clinical trial: NCT02400151.

In older populations, falls are responsible for decrease autonomy and increased pain and injuries. With aging, fall risk is multifactorial and associated with sarcopenia, impaired balance, falls themselves and psychological factors such as fear of falling. The objectives of the present study were: (a) to test the effects of a short multicomponent physical exercise program on fall risk and fear of falling; and (b) to analyze the relationship between fall risk and fear of falling. The participants were thirty-five older persons who were engaged in an eight-session physical exercise program. Balance (i.e., One-leg Balance Test, and Functional Reach Test), lower-limb endurance (i.e., Wall-sit Test) and fear of falling were measured before and after the multicomponent physical exercise program. Results indicated an increase in balance and a diminution of fear of falling after the end of the physical exercise program (p < 0.05). The program has an effect on lower limb endurance (p > 0.05). Gains in balance were correlated to the diminution of fear of falling (p < 0.05). An 8-week multicomponent physical exercise program based on balance is efficient to reduce fall risk and fear of falling among the elderly.

Even before the current pandemic, university students were known to have high levels of hassles, anxiety, and depressive symptoms. In all probability, the advent of COVID-19 has substantially raised these levels. The present study measured the emotional state of university students during lockdown and identified the relevant situational and psychological factors. To this end, 1,297 French university students were assessed during lockdown, which lasted from 16 March to 11 May in France. Situational factors included the belief that lockdown was compromising their future job prospects, COVID-19 symptoms, and health concerns. Psychological factors included students’ implicit theory of emotion, and the coping strategies they used during lockdown. We explored the extent to which these factors were associated with levels of hassles, anxiety, and depressive symptoms. Results indicated that students’ belief that lockdown was compromising their future job prospects was positively related to hassles ( r = .34, p < .001), while concerns about their own health and that of relatives were positively associated with anxiety ( r = .37 and .34; p < .001). In addition, use of the positive reframing coping strategy mediated the effect of students’ implicit theory of emotion on their depressive symptoms. Even though the national lockdown is now over, the pandemic will continue to have a major impact on university students over the coming months. It is therefore essential for universities to provide them with adequate psychological support.

In older populations, falls are responsible for decrease autonomy and increased pain and injuries. With aging, fall risk is multifactorial and associated with sarcopenia, impaired balance, falls themselves and psychological factors such as fear of falling. The objectives of the present study were: (a) to test the effects of a short multicomponent physical exercise program on fall risk and fear of falling; and (b) to analyze the relationship between fall risk and fear of falling. The participants were thirty-five older persons who were engaged in an eight-session physical exercise program. Balance (i.e., One-leg Balance Test, and Functional Reach Test), lower-limb endurance (i.e., Wall-sit Test) and fear of falling were measured before and after the multicomponent physical exercise program. Results indicated an increase in balance and a diminution of fear of falling after the end of the physical exercise program (

International audience; Many studies have highlighted the impact of lockdowns on the lifestyle of university students. We do not, however, know how these lifestyles have changed over the course of the COVID-19 pandemic. The objective of the present study was to describe changes in the levels of physical activity, sedentary behaviors, and alcohol consumption in French university students during different periods of the pandemic. This cohort study was conducted between 23 April and 11 December 2020. Measurements were performed four times: Twice during two successive lockdowns and twice during the intervening period. A total of 1294 university students were initially included, and 91 students completed the four measurement points over a seven-month period. Alcohol consumption, physical activity, and sedentary behaviors were measured. The results revealed high levels of physical activity during the first lockdown, but a subsequent decline during the pandemic that was partly explained by time. The pandemic had a positive effect on alcohol consumption. Sedentary levels were higher during both lockdowns, and sedentary behaviors tended to persist over time. This study raises concerns about the long-term effects of the pandemic on students’ health and lifestyle. The preponderance of distance learning should be reconsidered, given the negative impact of physical inactivity and sedentary behavior on long-term health, especially in young adults.

Points essentiels Les confinements ont augmente les symptomatologies anxieuses et depressives des etudiants Francais. Au-dela des confinements, la situation sanitaire a augmente la presence de symptomes anxieux chez les etudiants. Il semble que les etudiants aient augmente leur temps d’activite physique et sportive durant le premier confinement, mais que cela ne soit pas maintenu dans le temps, meme lors du second confinement. La crise sanitaire a eu pour consequence d’augmenter les comportements sedentaires. Il est important pour les universites d’accompagner les etudiants dans la gestion de leurs emotions et de leur mode de vie. Dans ce manuscrit, des dispositifs innovants mis en place par l’universite de Nimes seront presentes.

The increased prevalence and adverse health consequences of obesity have made it one of the leading public health issues in recent years. Importantly, several epidemiological studies have revealed significant associations between BMI and organic food consumption. However, although these studies have suggested that this factor holds promise to prevent obesity, they all suffer from methodological limitations, including self-reporting methods to assess BMI, not controlling for potential confounding factors or using a non-representative sample. Moreover, all were restricted to an adult sample. We present the results of a cross-sectional epidemiological study assessing the association of organic food consumption with BMI and obesity in a representative lifespan French sample (INCA3 study). Objective methods were used to measure BMI, and several potentially confounding variables were controlled for. In total, 1775 children and adolescents and 2121 adults underwent anthropometric measurements and completed questionnaires concerning their dietary habits and lifestyle. Unadjusted models systematically revealed negative associations between organic food consumption and both BMI and obesity across all age groups. These associations tended to remain statistically significant even after controlling for several confounding variables concerning socio-economic status, quality of the diet and physical activity. The effect sizes were, however, small. These data confirm the association between organic food consumption and obesity during both childhood and adulthood. Evidence from randomised controlled trials is required to investigate causality between organic food consumption and lower BMI or obesity rate.

Falls can have multiple detrimental consequences in the elderly, and this is particularly relevant for women. To prevent the risk of falling, intervention programmes based on physical exercises focusing on balance appear to be the most efficient, which explains the multiplication of this type of action at the local level. However, these actions are very rarely evaluated.Our sample consists of 26 women (75.0 ± 6.7 years old), randomly assigned to two groups: an intervention group (GI) that has benefited from a balance-oriented adapted physical activity (APA) program focused on balance and conducted in an associative structure; and a control group (GC). Our study aims to evaluate different parameters such as physical (functional mobility, balance), subjective (balanced confidence) and health (quality of life) indicators in women over 65 years of age, living independently at home.In people completing the program, we observed an improvement in equilibrium capabilities (significant increase in POMA score; p0.05), in balance and functional mobility (significant decrease in TUG score; p0.01) and in balance confidence (significant increase in ABC-S; p0.05).The implementation of a short programme by the associative structure seems to be an interesting approach for the prevention of falls in autonomous elderly women.

Obesity in children is associated with vitamin D (VD) deficiency and cardiometabolic abnormalities. To analyze the effects of VD supplementation in adolescents with obesity enrolled in a weight-loss program. Adolescents with obesity (n=26) and with normal weight (n=23; controls) were matched for age, sex, and puberty stage. The obesity group followed a 3-month weight-loss program that combined a reduced caloric intake with interval training physical activity and during which they received or not VD supplementation (4000 IU/d) (n=13/group; random assignation). The anthropometric parameters (BMI z-score, fat mass); serum levels of 25(OH)D, calcium and parathyroid hormone (PTH), cardiometabolic factors (triglycerides, HDL, and LDL cholesterol), fasting glucose and insulin, and homeostasis model assessment of insulin resistance index; diastolic, systolic and mean blood pressure, and inflammatory status (C-reactive protein, CRP) were measured at baseline and at the end of the 3-month program. At baseline, 25(OH)D concentration was lower and VD insufficiency (25(OH)D levels 50 nmol in all adolescents with obesity, but only in 46% of normal-weight adolescents. Moreover, the weight-loss program improved the cardiometabolic factors, inflammatory status (CRP) and physical performance, but VD supplementation did not have any additional effect. Analysis only of the adolescents with obesity and VD deficiency (25(OH)D

Resume Introduction Malgre l’importante prevalence de la symptomatologie depressive chez les femmes en surpoids ou en situation d’obesite, le role de la stigmatisation et des attributions causales dans l’expression de ces symptomes chez des femmes francaises a ete jusqu’ici largement sous-explore. Objectif Cette recherche a pour objectif d’etudier le role de la stigmatisation interiorisee, des experiences stigmatisantes et de l’attribution causale dans l’intensite des symptomes depressifs chez des femmes francaises en surpoids ou en situation d’obesite. Methode Ces quatre variables ont ete mesurees aupres de 160 femmes francaises en surpoids ou en situation d’obesite. Resultats Nos analyses mettent en evidence des correlations positives entre experiences stigmatisantes, stigmatisation interiorisee et symptomatologie depressive. Il est important de relever que les experiences stigmatisantes semblent jouer un role plus preponderant que la stigmatisation interiorisee dans l’expression des symptomes depressifs. Conclusion Pour les femmes presentant une symptomatologie depressive elevee, il apparait essentiel d’integrer a leurs prises en charge des interventions visant a reduire leur niveau de stigmatisation. En outre, dans une perspective preventive, il semble egalement primordial d’engager des campagnes en France visant a reduire la stigmatisation a l’encontre de cette population.

International audience; Scavenger receptors (SRs) like cluster determinant 36 (CD36) and SR class B type I (SR-BI) play a debated role in lipid transport across the intestinal brush border membrane. We used surface plasmon resonance to analyze real-time interactions between the extracellular protein loops and various ligands ranging from single lipid molecules to mixed micelles. Micelles mimicking physiological structures were necessary for optimal binding to both the extracellular loop of CD36 (lCD36) and the extracellular loop of SR-BI (lSR-BI). Cholesterol, phospholipid, and fatty acid micellar content significantly modulated micelle binding to and dissociation from the transporters. In particular, high phospholipid micellar concentrations inhibited micelle binding to both receptors (−53.8 and −74.4% binding at 0.32 mM compared with 0.04 mM for lCD36 and lSR-BI, respectively, P < 0.05). The presence of fatty acids was crucial for micelle interactions with both proteins (94.4 and 81.3% binding with oleic acid for lCD36 and lSR-BI, respectively, P < 0.05) and fatty acid type substitution within the micelles was the component that most impacted micelle binding to the transporters. These effects were partly due to subsequent modifications in micellar size and surface electric charge, and could be correlated to micellar vitamin D uptake by Caco-2 cells. Our findings show for the first time that micellar lipid composition and micellar properties are key factors governing micelle interactions with SRs.

International audience; Scope: A single nucleotide polymorphism in the cluster determinant 36 (CD36) gene has recently been associated with plasma alpha-tocopherol concentration, suggesting a possible role of this protein in vitamin E intestinal absorption or tissue uptake. Methods and results: To investigate the involvement of CD36 in vitamin E transport, we first evaluated the effect of CD36 on alpha- and gamma-tocopherol transmembrane uptake and efflux using transfected HEK cells. gamma-Tocopherol postprandial response was then assessed in CD36-deficient mice compared with wild-type mice, after the mice had been fully characterized for their alpha -tocopherol, vitamin A and lipid plasma, and tissue contents. Both alpha- and gamma-tocopherol uptake was significantly increased in cells overexpressing CD36 compared with control cells. Compared with wild-typemice, CD36-deficient mice displayed a significantly decreased cholesterol hepatic concentration, and males exhibited significantly higher triacylglycerol contents in liver, brain, heart, and muscle. Although tissue alpha -tocopherol concentration after adjustment for lipid content was not modified, gamma-tocopherol postprandial response was significantly increased in CD36-deficient mice compared with controls, likely reflecting the postprandial hypertriglyceridemia observed in these mice. Conclusion: Our findings show for the first time that CD36 participates-directly or indirectly-in vitamin E uptake, and that CD36 effect on postprandial lipid metabolism in turn modifies vitamin E postprandial response.

International audience; Background: Most people require dietaryvitamin D to achieve the recommended concentration of 25-hydroxyvitamin D [25(OH)D] in the blood. However, the response to vitamin D supplementation is highly variable among individuals. Objective: We assessed whether the variability in cholecalciferol bioavailability was associated with single-nucleotide polymorphisms (SNPs) in candidate genes. Methods: In a single-group design, 39 healthy adult men with a mean +/- SD age of 33 +/- 2 y and mean +/- SD body mass index lid kg/m(2)) of 22.9 +/- 0.3 were genotyped with the use of whole-genome microarrays. After an overnight fast, plasma 25(OH)D status was measured, and the subjects then consumed a meal that provided 5 mg cholecalciferol as a supplement. Plasma chylomicron cholecalciferol concentration was measured over 8 h, and cholecalciferol response was assessed by calculating the postprandial area under the curve. Partial least squares regression was used to test the association of SNPs in or near candidate genes (61 genes representing 3791 SNPs) with the postprandial cholecalciferol response. Results: The postprandial chylomicron cholecalciferol concentration peaked at 5.4 h. The cholecalciferol response was extremely variable among individuals (CV: 47%). It correlated with the chylomicron triglyceride (TG) response (r = 0.60; P < 0.001) but not with the fasting plasma 25(OH)D concentration (r = 0.04; P = 0.83). A significant (P = 1.32 x 10(-4)) partial least squares regression model that included 17 SNPs in 13 genes (including 5 that have been associated with chylomicron TG response) was associated with the variance in the cholecalciferol response. Conclusion: In healthy men, there is a high interindividual variability in cholecalciferol bioavailability that is associated with a combination of SNPs located in or near genes involved in both vitamin D and lipid metabolism. This trial was registered at clinicaltrials.gov as NCT02100774.

Introduction et but de l’etude Une part significative de la vitamine D presente dans l’organisme humain est produite au niveau de la peau par exposition a la lumiere ultraviolette. Neanmoins, pour obtenir ou maintenir un statut en vitamine D satisfaisant, une majorite d’individus doit consommer de la vitamine D, soit incluse dans l’alimentation, soit sous forme de supplements. Il a ete montre que la reponse sanguine a la supplementation en vitamine D presentait une forte variabilite interindividuelle. En outre, le transport de la vitamine D est en partie dependant de proteines. Enfin, nous avons montre que la biodisponibilite d’autres micronutriments lipidiques (tocopherol, luteine, lycopene et beta-carotene), qui possedent des mecanismes d’absorption en commun avec le cholecalciferol (D3), etait en partie modulee par des polymorphismes mononucleotidiques (SNPs) dans des genes impliques dans le transport intestinal de ces micronutriments et dans le metabolisme des chylomicrons. L’objectif principal de cette etude etait donc d’identifier des SNPs associes avec la variabilite interindividuelle de la biodisponibilite de la D3. Materiel et methodes Trente-neuf hommes adultes en bonne sante ont ete genotypes a l’aide de puces a ADN genome entier. Ils ont consomme un repas contenant 5 g de D3 sous forme de supplement. La concentration en D3 et en calcifediol (25(OH)D) dans les chylomicrons plasmatiques a ete mesuree a intervalles de temps reguliers jusqu’a 8 h apres le repas. L’association entre des SNPs dans des genes impliques dans le metabolisme de la vitamine D et des lipides (61 genes candidats representant 3791 SNPs) et la reponse postprandiale en D3 dans les chylomicrons a ete analysee par regression des moindres carres partiels (regression PLS). Resultats La concentration postprandiale en D3 des chylomicrons a atteint son maximum 5,4 h apres le repas. Nous n’avons pas observe de variation significative de la concentration postprandiale en 25(OH)D des chylomicrons. La reponse postprandiale en D3 dans les chylomicrons presentait une forte variabilite interindividuelle (CV = 47 %). Cette reponse etait positivement correlee a la reponse postprandiale en triglycerides (r = 0,60, p Conclusion Chez des hommes adultes en bonne sante, on observe une forte variabilite interindividuelle de la biodisponibilite de la D3. Cette variabilite est associee avec une combinaison de SNPs dans des genes impliques dans le metabolisme de la vitamine D et des lipides.

Equipe ASMS; International audience; Enriching oils, such as olive oil, could be one solution to tackle the worldwide epidemic of vitamin D deficiency and to better fit with omega 3 (DHA) recommendations. However, data regarding the interactions occurring at the intestinal level between vitamin D and phenols from olive oil are scarce. We first determined the effect of polyphenols from a virgin olive oil, and a virgin olive oil enriched with DHA, on vitamin D absorption in rats. We then investigated the effects of 3 main olive oil phenols (oleuropein, hydroxytyrosol and pinoresinol) on vitamin D uptake by Caco-2 cells. The presence of polyphenols in the olive oil supplemented with DHA inhibited vitamin D postprandial response in rats (-25%, p < 0.05). Similar results were obtained with a mix of the 3 polyphenols delivered to Caco-2 cells. However, this inhibitory effect was due to the presence of pinoresinol only. As the pinoresinol content can highly vary between olive oils, the present results should be taken into account to formulate an appropriate oil product enriched in vitamin D

International audience; The interactions occurring at the intestinal level between the fat-soluble vitamins A, D, E and K (FSVs) are poorly documented. We first determined each FSV absorption profile along the duodenal-colonic axis of mouse intestine to clarify their respective absorption sites. We then investigated the interactions between FSVs during their uptake by Caco-2 cells. Our data show that vitamin A was mostly absorbed in the mouse proximal intestine, while vitamin D was absorbed in the median intestine, and vitamin E and K in the distal intestine. Significant competitive interactions for uptake were then elucidated among vitamin D, E and K, supporting the hypothesis of common absorption pathways. Vitamin A also significantly decreased the uptake of the other FSVs but, conversely, its uptake was not impaired by vitamins D and K and even promoted by vitamin E. These results should be taken into account, especially for supplement formulation, to optimise FSV absorption.

International audience; Food fortification is a strategy to overcome vitamin A deficiency in developing countries. Our aim was to investigate the involvement of the bovine milk protein beta-lactoglobulin (beta-Lg), a potential retinoid carrier, in vitamin A absorption. In vivo experiments were conducted by force-feeding mice with retinol or beta-carotene associated with either beta-Lg or oil-in-water emulsion, with subsequent determination of both vitamin A intestinal mucosa and plasma contents. Caco-2 cells were then used to investigate the mechanisms of vitamin A uptake when delivered by either beta-Lg or mixed micelles. We showed that beta-Lg was as efficient as emulsion to promote beta-carotene, but not retinol, absorption in mice. Similar results were obtained in vitro. Interestingly, an inhibitor of the Scavenger Receptor Class B Type I significantly decreased the uptake of micellar beta-carotene but not that of beta-carotene bound to beta-Lg. Overall, we showed that beta-Lg would be a good vector for beta-carotene food fortification.

International audience; Vitamin K-1 (phylloquinone) intestinal absorption is thought to be mediated by a carrier protein that still remains to be identified. Apical transport of vitamin K-1 was examined using Caco-2 TC-7 cell monolayers as a model of human intestinal epithelium and in transfected HEK cells. Phylloquinone uptake was then measured ex vivo using mouse intestinal explants. Finally, vitamin K-1 absorption was compared between wild-type mice and mice overexpressing scavenger receptor class B type I (SR-BI) in the intestine and mice deficient in cluster determinant 36 (CD36). Phylloquinone uptake by Caco-2 cells was saturable and was significantly impaired by co-incubation with alpha-tocopherol (and vice versa). Anti-human SR-BI antibodies and BLT1 (a chemical inhibitor of lipid transport via SR-BI) blocked up to 85% of vitamin K-1 uptake. BLT1 also decreased phylloquinone apical efflux by similar to 80%. Transfection of HEK cells with SR-BI and CD36 significantly enhanced vitamin K-1 uptake, which was subsequently decreased by the addition of BLT1 or sulfo-N-succinimidyl oleate (CD36 inhibitor), respectively. Similar results were obtained in mouse intestinal explants. In vivo, the phylloquinone postprandial response was significantly higher, and the proximal intestine mucosa phylloquinone content 4 h after gavage was increased in mice overexpressing SR-BI compared with controls. Phylloquinone postprandial response was also significantly increased in CD36-deficient mice compared with wild-type mice, but their vitamin K-1 intestinal content remained unchanged. Overall, the present data demonstrate for the first time that intestinal scavenger receptors participate in the absorption of dietary phylloquinone.

International audience; Scavenger receptor class B type I (SR-BI) and cluster determinant 36 (CD36) have been involved in cellular uptake of some provitamin A carotenoids. However, data are incomplete (e.g., there are no data on a-carotene), and it is not known whether genetic variants in their encoding genes can affect provitamin A carotenoid status. The objectives were 1) to assess the involvement of these scavenger receptors in cellular uptake of the main provitamin A carotenoids (i.e., beta-carotene, alpha-carotene, and beta-cryptoxanthin) as well as that of preformed vitamin A (i.e., retinol) and 2) to investigate the contribution of genetic variations in genes encoding these proteins to interindividual variations in plasma concentrations of provitamin A carotenoids. The involvement of SR-BI and CD36 in carotenoids and retinol cellular uptake was investigated in Caco-2 and human embryonic kidney (HEK) cell lines. The involvement of scavenger receptor class B type I (SCARB1) and CD36 genetic variants on plasma concentrations of provitamin A carotenoids was assessed by association studies in 3 independent populations. Cell experiments suggested the involvement of both proteins in cellular uptake of provitamin A carotenoids but not in that of retinol. Association studies showed that several plasma provitamin A carotenoid concentrations were significantly different (P < 0.0083) between participants who bore different genotypes at single nucleotide polymorphisms and haplotypes in CD36 and SCARB1. In conclusion, SR-BI and CD36 are involved in cellular uptake of provitamin A carotenoids, and genetic variations in their encoding genes may modulate plasma concentrations of provitamin A carotenoids at a population level. J. Nutr. 143: 448-456, 2013.

International audience; We have recently shown that vitamin D-3 (cholecalciferol) absorption is not a simple passive diffusion but involves cholesterol transporters. As free fatty acids (FAs) modulate cholesterol intestinal absorption and metabolism, we hypothesized that FAs may also interact with vitamin D absorption. Effects of FAs were evaluated at different levels of cholecalciferol intestinal absorption. First, the physicochemical properties of micelles formed with different FAs were analyzed. The micelles were then administered to human Caco-2 cells in culture to evaluate FA effects on (i) cholecalciferol uptake and basolateral efflux and (ii) the regulation of genes coding proteins involved in lipid absorption process. Micellar electric charge was correlated with both FA chain length and degree of unsaturation. Long-chain FAs at 500 mu M in mixed micelles decreased cholecalciferol uptake in Caco-2 cells. This decrease was annihilated as soon as the long-chain FAs were mixed with other FAs. Oleic acid significantly improved cholecalciferol basolateral efflux compared to other FAs. These results were partly explained by a modulation of genes coding for lipid transport proteins such as Niemann-pick C1-like 1 and scavenger receptor class B type I. The data reported here show for the first time that FAs can interact with cholecalciferol intestinal absorption at different key steps of the absorption process. Cholecalciferol intestinal absorption may thus be optimized according to oil FA composition. (c) 2013 Elsevier Inc. All rights reserved.

The intestinal absorption of cholesterol and lipid micronutrients such as vitamin E has been shown to share some common pathways. The present study aims to further compare the uptake of cholesterol ([3H]cholesterol v. 22-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-23,24-bisnor-5-cholen-3-ol (NBD-cholesterol)) and tocopherol in Caco-2 TC-7 cells and in mouse intestine, with special focus on the respective roles of scavenger receptor class B type I (SR-BI) and Niemann-Pick C1-like 1 (NPC1L1). Conversely to NBD-cholesterol, the uptakes of [3H]cholesterol and tocopherol by Caco-2 cells were impaired by both block lipid transport-1 and ezetimibe, which inhibit SR-BI and NPC1L1, respectively. These inhibitions occurred only when cholesterol or tocopherol was delivered to cells included in micelles that contained biliary acid and at least oleic acid as a lipid. In vivo, after 2 h of digestion in mice, the uptake of the two cholesterol analogues and of tocopherol all showed distinct patterns along the duodenum–jejunum axis. [3H]Cholesterol uptake, which correlated closely to NPC1L1 mRNA expression in wild-type (wt) mice, was strongly inhibited by ezetimibe. Intestinal SR-BI overexpression did not change NPC1L1 expression and led to a significant increase in [3H]cholesterol uptake in the distal jejunum. Conversely, neither ezetimibe treatment nor SR-BI overexpression had an effect on NBD-cholesterol uptake. However, in contrast with SR-BI mRNA expression, tocopherol absorption increased strongly up to the distal jejunum in wt mice where it was specifically inhibited by ezetimibe, and was increased in the proximal intestine of intestinal SR-BI-overexpressing mice. Thus, cholesterol and tocopherol uptakes share common pathways in cell culture models, but display different in vivo absorption patterns associated with distinct contributions of SR-BI and NPC1L1.

International audience; Scope: Adequate vitamin D status is necessary and beneficial for health, although deficiency and insufficiency are very common. As cholecalciferol (vitamin D3) structure is close to cholesterol structure, we hypothesized that phytosterols, frequently used to decrease cholesterol, intestinal absorption and consequently to reduce hypercholesterolemia, may also interact with cholecalciferol absorption. Methods and results: β-Sitosterol effect on cholecalciferol postprandial response was first assessed in mice. We then evaluated the effect of different sterols on (i) cholecalciferol micellar incorporation, (ii) cholecalciferol apical uptake and (iii) basolateral efflux in vitro or ex vivo. In mice, cholecalciferol bioavailability was 15-fold lower in the presence of β-sitosterol (p

International audience; Scope: It is assumed that vitamin D is absorbed by passive diffusion. However, since cholecalciferol (vitamin D(3) ) and cholesterol display similar structures, we hypothesized that common absorption pathways may exist. Methods and results: Cholecalciferol apical transport was first examined in human Caco-2 and transfected Human embryonic kidney (HEK) cells. Cholecalciferol uptake was then valuated ex vivo and in vivo, using either wild-type mice, mice overexpressing Scavenger Receptor class B type I (SR-BI) at the intestinal level or mice treated or not with ezetimibe. Cholecalciferol uptake was concentration-, temperature- and direction-dependent, and was significantly impaired by a co-incubation with cholesterol or tocopherol in Caco-2 cells. Moreover Block Lipid Transport-1 (SR-BI inhibitor) and ezetimibe glucuronide (Niemann-Pick C1 Like 1 inhibitor) significantly decreased cholecalciferol transport. Transfection of HEK cells with SR-BI, Cluster Determinant 36 and Niemann-Pick C1 Like 1 significantly enhanced vitamin D uptake, which was significantly decreased by the addition of Block Lipid Transport-1, sulfo-N-succinimidyl oleate (Cluster Determinant 36 inhibitor) or ezetimibe glucuronide, respectively. Similar results were obtained in mouse intestinal explants. In vivo, cholecalciferol uptake in proximal intestinal fragments was 60% higher in mice overexpressing SR-BI than in wild-type mice (p

Interactions lipides-proteines membranaires : nouvelles donnees sur l’implication de SR-BI et CD36 dans l’absorption intestinale des lipides grâce la resonnance plasmonique de surface. 11. Journees Francophones de Nutrition (JFN)

Introduction et but de l’etude Une concentration postprandiale elevee en chylomicrons, qui sont essentiellement constitues de triglycerides (TG) issus des lipides nouvellement absorbes, est associee a un risque accru de developper des maladies cardiovasculaires et l’atherosclerose. On observe une forte variabilite interindividuelle de ce parametre, due en partie a des polymorphismes mononucleotidiques (SNPs) dans des genes impliques dans le metabolisme des lipides. Les etudes existantes ne se sont jusqu’ici interessees qu’a des SNPs analyses individuellement, et qui n’expliquent en consequence qu’une faible partie de cette variabilite. Dans cette etude, nous avons cherche a identifier une combinaison de SNPs associee a la variabilite de la reponse postprandiale en TG des chylomicrons suite a l’ingestion d’un repas riche en lipides. Materiel et methodes Trente-trois hommes adultes (IMC = 23,1 ± 0,4 kg/m 2 ) en bonne sante et non dyslipidemiques ont ete genotypes a l’aide de puces a ADN genome entier. Ils ont consomme a quatre occasions un repas riche en lipides et leur concentration plasmatique en TG des chylomicrons a ete mesuree a intervalles de temps reguliers jusqu’a 8h apres la consommation des repas. La moyenne des aires sous la courbe de cette concentration suite aux 4 repas a ete calculee afin d’evaluer la reponse postprandiale en TG des chylomicrons de chaque sujet, et de controler ainsi la variabilite intra-individuelle. Nous avons ensuite utilise une approche statistique multivariee, la regression des moindres carres partiels (PLS regression) , pour analyser l’association de plus de 6000 SNPs, dans 126 genes candidats lies au metabolisme des lipides, avec la variabilite de la reponse postprandiale en TG des chylomicrons. Resultats et Analyse statistique Nous avons identifie un modele valide ( p = 1,3 x 10 −7 ), comportant 42 SNPs dans 23 genes (ABCA1, APOA1, APOA5, APOB, BET1, CD36, COBLL1, ELOVL5, FRMD5, GPAM, INSIG2, IRS1, LDLR, LIPC, LPL, LYPLAL1, MC4R, NAT2, PARK2, SLC27A5, SLC27A6, TCF7L2, ZNF664) , qui permet d’expliquer la reponse postprandiale en TG des chylomicrons d’un sujet avec une erreur de 14 % seulement. Pour 39 de ces SNPs, les sujets possedant des genotypes differents presentaient une reponse postprandiale en TG des chylomicrons significativement differente (p-value corrigee Conclusion Ce modele predictif necessite d’etre valide dans d’autres groupes de sujets et sera certainement ameliore. Mais cette approche pourrait permettre de predire la reponse postprandiale en TG des chylomicrons avec un simple genotypage, ce qui serait nettement moins couteux que plusieurs tests de charge lipidiques. Les sujets a risque pourraient ainsi beneficier de conseils nutritionnels visant a diminuer leur risque cardiovasculaire en diminuant leurs apports en matieres grasses.

Introduction et but de l’etude Les recepteurs eboueurs tels que le Cluster Determinant 36 (CD36) et le Scavenger Receptor class B type I (SR-BI) jouent un role controverse dans le transport des lipides au travers de la bordure en brosse des enterocytes. Afin de mieux comprendre le fonctionnement de CD36 et de SR-BI, nous avons utilise la resonance plasmonique de surface permettant d’etudier les interactions entre ces transporteurs et de nombreux ligands lipidiques. Materiel et methodes Les boucles extracellulaires des transporteurs membranaires SR-BI et CD36 ont ete fixees sur des « Sensor chips » ou membranes NTA (nitrilotriacetic acid) par l’intermediaire d’une etiquette poly-histidine. Les interactions en temps reel entre les ligands proteines et les analytes lipidiques (allant de la molecule isolee a des structures plus physiologiques comme des micelles mixtes synthetiques) ont ete explorees grâce a l’utilisation d’un Biacore T100. Resultats et Analyse statistique Nous avons montre que les micelles imitant des conditions physiologiques, i.e. contenant diverses especes de lipides et de produits de digestion des lipides, sont necessaires a une association micellaire optimale a CD36 et SR-BI. Nous avons aussi montre que le contenu en cholesterol, phospholipides et en acides gras modulait significativement l’association et la dissociation des micelles aux recepteurs. En particulier, les fortes concentrations en phospholipides inhibaient l’association aux transporteurs (−53,8% et −74,4 % a 0,32 mM par rapport a 0,04 mM pour CD36 et SR-BI, respectivement, P Conclusion Nos donnees montrent pour la premiere fois que les recepteurs CD36 et SR-BI peuvent fixer efficacement les micelles mixtes et que la composition lipidique, et les proprietes physicochimiques des micelles sont des facteurs cles gouvernant les interactions micellaires avec les recepteurs eboueurs intestinaux.

International audience