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Phytofluene is a colorless carotenoid with potential health benefits that displays a higher bioavailability compared to carotenoids such as lutein, β-carotene or lycopene. Several studies suggest its bioavailability displays an elevated interindividual variability. The aim of this work is to investigate whether a combination of SNPs is associated with this variability.Thirty-seven healthy adult males consume a test meal that provided phytofluene from a tomato puree. Phytofluene concentrations are measured at fast and in chylomicrons at regular time intervals after meal intake. Identification of the combination of SNPs that best explained the interindividual variability of the phytofluene response is assessed by partial least squares regression. There is a large interindividual variability in the phytofluene response, with CV = 88%. Phytofluene bioavailability is positively correlated with fasting plasma phytofluene concentration (r = 0.57; p = 2 × 10This study reports a combination of SNPs that is associated with a significant part of the interindividual variability of phytofluene bioavailability in a healthy male adult population.

International audience; Purpose1) To test the hypothesis of the existence of a perinatal vitamin A (VA) programming of VA metabolism and to better understand the intestinal regulation of VA metabolism.MethodsOffspring from rats reared on a control (C) or a VA-deficient (D) diet from 6 weeks before mating until offspring weaning, i.e., 7 weeks after mating, were themselves reared on a C or D diet for 19 weeks, resulting in the following groups: C–C (parents fed C—offspring fed C), D-C, C-D and D-D. VA concentrations were measured in plasma and liver. β-Carotene bioavailability and its intestinal conversion rate to VA, as well as vitamin D and E bioavailability, were assessed after gavages with these vitamins. Expression of genes involved in VA metabolism and transport was measured in intestine and liver.ResultsC–D and D–D had no detectable retinyl esters in their liver. Retinolemia, hepatic retinol concentrations and postprandial plasma retinol response to β-carotene gavage were higher in D–C than in C–C. Intestinal expression of Isx was abolished in C–D and D–D and this was concomitant with a higher expression of Bco1, Scarb1, Cd36 and Lrat in males receiving a D diet as compared to those receiving a C diet. β-Carotene, vitamin D and E bio-availabilities were lower in offspring receiving a D diet as compared to those receiving a C diet.ConclusionA VA-deficient diet during the perinatal period modifies the metabolism of this vitamin in the offspring. Isx-mediated regulation of Bco1 and Scarb1 expression exists only in males severely deficient in this vitamin. Severe VA deficiency impairs β-carotene and vitamin D and E bioavailability.

Dietary intake and tissue levels of carotenoids have been associated with a reduced risk of several chronic diseases, including cardiovascular diseases, type 2 diabetes, obesity, brain-related diseases and some types of cancer. However, intervention trials with isolated carotenoid supplements have mostly failed to confirm the postulated health benefits. It has thereby been speculated that dosing, matrix and synergistic effects, as well as underlying health and the individual nutritional status plus genetic background do play a role. It appears that our knowledge on carotenoid-mediated health benefits may still be incomplete, as the underlying mechanisms of action are poorly understood in relation to human relevance. Antioxidant mechanisms – direct or via transcription factors such as NRF2 and NF-κB – and activation of nuclear hormone receptor pathways such as of RAR, RXR or also PPARs, via carotenoid metabolites, are the basic principles which we try to connect with carotenoid-transmitted health benefits as exemplified with described common diseases including obesity/diabetes and cancer. Depending on the targeted diseases, single or multiple mechanisms of actions may play a role. In this review and position paper, we try to highlight our present knowledge on carotenoid metabolism and mechanisms translatable into health benefits related to several chronic diseases.

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International audience; Consumption of diets rich in fruits and vegetables, which provide some fat-soluble vitamins and many phyto-chemicals, is associated with a lower risk of developing certain degenerative diseases. It is well accepted that not only the parent compounds, but also their derivatives formed upon enzymatic or nonenzymatic transformations, can produce protective biological effects. These derivatives can be formed during food storage, processing, or cooking. They can also be formed in the lumen of the upper digestive tract during digestion, or via metabolism by microbiota in the colon. This review compiles the known metabolites of fat-soluble vitamins and fat-soluble phytochemicals (FSV and FSP) that have been identified in food and in the human digestive tract, or could potentially be present based on the known reactivity of the parent compounds in normal or pathological con-ditions, or following surgical interventions of the digestive tract or consumption of xenobiotics known to impair lipid absorption. It also covers the very limited data available on the bioavailability (absorption, intestinal mucosa metabolism) and summarizes their effects on health. Notably, despite great interest in identifying bioactive derivatives of FSV and FSP, studying their absorption, and probing their putative health effects, much research remains to be conducted to understand and capitalize on the potential of these molecules to preserve health.

Conférence en ligne aux Journées Francophones de Nutrition - JFN du 10 au 12/11/2021.; International audience; In urban and peri-urban areas, where waste management is more than ever a major issue, insect farming may be an ecological way to recycle bio-waste in a circular bioeconomy approach. Indeed, someinsect species such as Hermetia illucens can grow on many types of organic substrates and can convert them into valuable byproducts(1). There may be a wide variety of insect bioconversion products since larvae are a natural source of micronutrients, amino acids and antimicrobial compounds. They are also rich in proteins which can be used for animal feed, in fats used for the production of biodiesel, in chitin used in various industries, and they produce a type of manure called frass that can be used as biofertilizer(2). However, besides its ecological and nutritional benefits, risks of insectbased bioconversion should be identified and monitored. Indeed, some chemical contaminants may be found in insect farming environment, in their feeding substrates or can be produced during processing methods(3). Moreover, microbiological contaminants may be found in the farming insect chain(4). Therefore, it is necessary to assess the impact of these contaminants on insect survival and to determine their fate in the insect. It is also important to assess the environmental, social and economic impact of insect-based bioconversion and to determine the consumer acceptability of these new processes and products

International audience; Food matrix interactions with polyphenols can affect their bioavailability and as a consequence may modulate their biological effects. The aim of this study was to determine if the matrix and its processing would modulate the bioavailability and the postprandial nutrigenomic response to a dietary inflammatory stress of apple flavan-3-ol monomers. We carried out an acute randomized controlled study in minipigs challenged with a high fat meal (HFM) supplemented with raw fruit, puree, or apple phenolic extract with matched content of flavan-3-ol monomers. Fasting and postprandial blood samples were collected over 3 h to quantify flavan-3-ol monomers in sera by UPLC-Q-TOF/MS and to isolate peripheral blood mononuclear cells (PBMCs) for assessing the changes in the gene expression profile using a microarray analysis. When compared to the extract-supplemented meal, the peak of the total flavan-3-ol concentration was reduced by half with both raw apple and puree supplements. The apple matrices also affected the gene expression profile as revealed by the Principal Component Analysis of the microarray data from PBMCs which discriminated the supplementation of HFM with the polyphenol extract from those with raw apples or puree. A total of 309 genes were identified as differentially expressed by the apple-derived products compared to HFM, with 63% modulated only in the presence of the food matrix (apple and puree). The number of differentially modulated genes was higher with the puree (246) than with the unprocessed apple (182). Pathway enrichment analyses revealed that genes affected by the apple-derived products control inflammation and leukocyte transendothelial migration both involved in the onset of atherosclerotic processes. Overall, this study showed that the two apple matrices reduce the postprandial serum concentration of flavon-3-ols whereas they increase the nutrigenomic response of PBMCs. The biological processes identified as modulated by the apple products suggest an attenuation of the transient proinflammatory response induced by a HFM. The differences observed between the nutrigenomic responses support that the apple matrix and its processing affect the nutrigenomic response, probably by increasing the bioavailability of other apple phytochemicals. To conclude, this study raises awareness for considering the impact of the food matrix and its processing on the biological response of polyphenols in nutritional studies.

International audience; Carotenoids are lipophilic phytochemicals; their intake has been associated with reduced chronic diseases. However, their absorption depends on emulsification during digestion and incorporation into mixed micelles, requiring digestive enzymes, gastric peristalsis, bile, and dietary lipids. In this study, we investigated whether whey-protein-isolate (WPI), a commonly consumed protein source, can modulate β-carotene bioaccessibility in vitro, especially under incomplete digestive conditions, i.e. under low digestive enzyme concentrations. Thus, amounts of pepsin, pancreatin, bile, co-digested lipids and kinetic energy and gastric digestion time were modified, and WPI at concentrations equivalent to 0/25/50% of the protein recommended dietary allowance (approx. 60 g/d) were added to β-carotene dissolved in oil. WPI enhanced bioaccessibility by up to 20% (p

Selenium (Se) is an essential micronutrient for human biology that executes its functions as the amino acid selenocysteine via selenoproteins, which have important functions in, for example, antioxidation, immunomodulation, thyroid metabolism, and human fertility. Se nutritional status is assessed using the quantification of blood Se biomarkers, which are influenced by several factors, including diet, age, gender, smoking status, alcohol consumption, health condition, and the genetic characteristics of individuals. Nutrigenetic studies have identified single nucleotide polymorphisms in selenoproteins that might clarify the high variability in values reported for biomarkers of Se nutritional status in different populations, and the response of these biomarkers to Se supplementation with either organic or inorganic forms of Se. This review aims to (1) define the basic aspects of Se biology, (2) describe the current most commonly used biomarkers of Se nutritional status, and (3) provide a summary of associations between functional single nucleotide polymorphisms in selenoproteins and biomarkers of Se status in healthy populations.

International audience; Fluorophore 2',7'-dichlorofluorescin (DCF) is the most frequently used probe for measuring oxidative stress in cells, but many aspects of DCF remain to be revealed. Here, DCF was used to study the Fenton reaction in detail, which confirmed that in a cell-free system, the hydroxyl radical was easily measured by DCF, accompanied by the consumption of H2O2 and the conversion of ferrous iron into ferric iron. DCF fluorescence was more specific for hydroxyl radicals than the measurement of thiobarbituric acid (TBA)-reactive 2-deoxy-D-ribose degradation products, which also detected H2O2. As expected, hydroxyl radical-induced DCF fluorescence was inhibited by iron chelation, anti-oxidants, and hydroxyl radical scavengers and enhanced by low concentrations of ascorbate. Remarkably, due to DCF fluorescence auto-amplification, Fenton reaction-induced DCF fluorescence steadily increased in time even when all ferrous iron was oxidized. Surprisingly, the addition of bovine serum albumin rendered DCF sensitive to H2O2 as well. Within cells, DCF appeared not to react directly with H2O2 but indirect via the formation of hydroxyl radicals, since H2O2-induced cellular DCF fluorescence was fully abolished by iron chelation and hydroxyl radical scavenging. Iron chelation in H2O2-stimulated cells in which DCF fluorescence was already increasing did not abrogate further increases in fluorescence, suggesting DCF fluorescence auto-amplification in cells. Collectively, these data demonstrate that DCF is a very useful probe to detect hydroxyl radicals and hydrogen peroxide and to study Fenton chemistry, both in test tubes as well as in intact cells, and that fluorescence auto-amplification is an intrinsic property of DCF.

International audience; Scope Cholesterol bioavailability displays a high interindividual variability, partly due to genetic factors. Existing studies have focused on single nucleotide polymorphisms (SNPs) analyzed individually, which only explained a minor fraction of the variability of this complex phenotype. The aim is to identify a combination of SNPs associated with a significant part of the variability in cholesterol bioavailability. Methods and results Thirty-nine healthy adult males are given a standard test snack containing 80 mg heptadeuterated (D7) cholesterol. The plasma D7-cholesterol concentration is measured at equilibrium 40 h after test snack intake. The D7-cholesterol response (D7-cholesterol/total cholesterol concentration) exhibits a relatively high interindividual variability (CV = 32%). The association of exonic SNPs in candidate genes (188 genes involved in or related to cholesterol metabolism) with the plasma D7-cholesterol response is assessed by univariate statistics followed by partial least squares regression. A significant model (p-value after cross-validation ANOVA = 1.64 x 10(-7)) that includes 8 SNPs (SOAT2-rs9658625,DNAH11-rs11768670,LIPC-rs690,MVK-rs2287218,GPAM-rs10787428,APOE-rs7412,CBS-rs234706, andWRN-rs1801196) explains 59.7% of the variance in cholesterol bioavailability (adjustedR(2)). Conclusion Here a combination of SNPs is significantly associated with the variability in dietary cholesterol bioavailability in healthy adult males.

International audience; We showed that black soldier fly larvae reared on fruits and vegetables rich in provitamin A carotenoids can accumulate significant amounts of these vitamin A precursors. Using a simulated gastro-intestinal digestion model, we demonstrated that α- and β-carotene from the larvae are as bioaccessible as from the fruits and vegetables they were reared on. We calculated that provitamin A carotenoid-rich larvae have the capacity to provide more vitamin A than fruits and vegetables rich in these molecules. Remarkably, the incorporation of usual quantities of these larvae in feed could cover the needs of several production animals for this vitamin. Thus, our findings suggest that rearing black soldier fly larvae on by-products or waste rich in provitamin A carotenoids could be a sustainable strategy to recycle a fraction of vitamin A back into the food chain and could represent a new approach to fight against vitamin A deficiency.

There is uncertainty regarding carotenoid intake recommendations, because positive and negative health effects have been found or are correlated with carotenoid intake and tissue levels (including blood, adipose tissue, and the macula), depending on the type of study (epidemiological vs intervention), the dose (physiological vs supraphysiological) and the matrix (foods vs supplements, isolated or used in combination). All these factors, combined with interindividual response variations (eg, depending on age, sex, disease state, genetic makeup), make the relationship between carotenoid intake and their blood/tissue concentrations often unclear and highly variable. Although blood total carotenoid concentrations, This research received support from the EU Cooperation in Science and Technology Action CA15136 EUROCAROTEN. Support was also received from the Instituto de Salud Carlos III (grant PI16/01991), co-funded by ERDF/European Social Fund.

International audience; Proteins could alter carotenoid bioaccessibility through altering their fate during digestion, due to emulsifying properties of resulting peptides, or influencing access of digestion enzymes to lipid droplets. In this investigation, we studied whether whey protein isolate (WPI), soy protein isolate (SPI), sodium caseinate (SC) and gelatin (GEL), added at various concentrations (expressed as percentage of recommended dietary allowance (RDA): 0, 10, 25 and 50%) would influence the bioaccessibility of lycopene, beta-carotene or lutein, added as pure carotenoids solubilized in oil, during simulated gastro-intestinal (GI) digestion. Protein and lipid digestion as well as selected physico-chemical parameters including surface tension, zeta-potential and micelle size were evaluated. Adding proteins influenced positively the bioaccessibility of beta-carotene, by up to 189% (p< 0.001), but it resulted in generally decreased bioaccessibility of lutein, by up to 50% (p< 0.001), while for lycopene, the presence of proteins did not influence its bioaccessibility, except for a slight increase with WPI, by up to 135% (p< 0.001). However, the effect depended significantly on the type of protein (p< 0.001) and its concentration (p< 0.001). While beta-carotene bioaccessibility was greatly enhanced in the presence of SC, compared to WPI and GEL, the presence of SPI strongly decreased carotenoid bioaccessibility. Neglecting individual carotenoids, higher protein concentration correlated positively with carotenoid bioaccessibility (R= 0.57,p< 0.01), smaller micelle size (R= -0.83,p< 0.01), decreased repulsive forces (zeta-potential,R= -0.72,p< 0.01), and higher surface tension (R= 0.44,p< 0.01). In conclusion, proteins differentially affected carotenoid bioaccessibility during digestion depending on carotenoid and protein species, with both positive and negative interactions occurring.

International audience; Functional foods containing dispersible phytosterols (DPs) are recommended to reduce cholesterol absorption in humans. However, only a few studies have been conducted on the effect of DP vehicles on carotenoid bioaccessibility and uptake by intestinal cells. On a previously developed fermented maize product containing both DPs and carotenoids, we aim to evaluate the effect of DPs encapsulated by maltodextrin on the carotenoid/phytosterol/cholesterol interactions during gastro-duodenal digestion. Thanks to maltodextrin properties, beta-carotene and lycopene bioaccessibilities were significantly improved by 40.2 +/- 1.4% while that of beta-cryptoxanthin decreased by 14 +/- 0.1%. Additionally, the presence of DPs reduced the cholesterol micellarization by 51.8 +/- 4.2%. Despite a slight decrease in carotenoid uptake caused by the DP vehicle, related to micelle size, an inhibition of cholesterol accumulation by Caco-2 cells was observed. These results highlighted the key role of maltodextrin as a vehicle of DPs on carotenoid and cholesterol absorption.

International audience; Scope The effect of vitamin A deficiency on vitamin A and lipid postprandial metabolism in young rats is addressed, considering the effect of sex. Methods and Results Sprague-Dawley rats are fed either 400 UI.kg(-1) vitamin A diet (vitamin A-deficient (VAD) diet) or 2300 UI.kg(-1) vitamin A (control diet), before being mated. Mothers receive the same VAD or control diet during gestation and lactation. Offspring receive the same diet than mothers until 8 weeks of age. VAD diet-fed female and male offspring display a severe vitamin A deficiency with no body weight or glucose tolerance defects. Fasting plasma triglyceride concentrations are decreased in VAD diet-fed animals compared to controls (p < 0.05). Retinyl ester postprandial responses after vitamin A gavage, expressed as area under the curves, are not different in VAD diet-fed and control animals, although retinyl ester postprandial peak is significantly delayed (p < 0.05) in VAD diet-fed rats. Lipids also accumulate in the distal part of the intestine after gavage and [1-C-13]-oleate postprandial response is decreased in VAD diet-fed males. Conclusion Vitamin A deficiency modulates both vitamin A absorption rate and lipid postprandial metabolism, which can partly explain the altered fasting lipid status observed in VAD diet-fed offspring.

Carotenoids 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.

International audience; PURPOSE:The consumption of Brazil nuts has been associated with benefits to lipid metabolism and reductions in total cholesterol and LDL concentrations. They are the richest natural source of selenium which has essential functions in human physiology. Genetic polymorphisms in Selenoprotein P could impair lipid and glucose metabolisms. The aim of this work was to verify the influence of polymorphisms in genes for selenoproteins on blood lipid levels after dietary supplementation with Brazil nuts in healthy adults.METHODS:The study included 130 healthy volunteers selected at the University of São Paulo, Brazil. They were supplemented with one nut a day for 8 weeks, followed by 8 weeks without intervention. The following analyses were performed: anthropometric measurements, serum fasting glucose, lipid profile, C-reactive protein and plasma MDA levels. The volunteers were genotyped for SNPs rs1050450, rs3811699, rs1800699, rs713041, rs3877899, rs7579, rs34713741, and rs5845 in genes for selenoproteins.RESULTS:The concentrations of total cholesterol and fasting glucose levels decreased after 8 weeks of supplementation (p < 0.05). Glucose levels were modulated by rs3877899 in SEPP1, with significantly lower levels observed for individuals with the GA + AA genotype (p = 0.025). In addition, rs7579 was associated with cholesterol concentrations, which were significantly lower for individuals with the GG genotype (p = 0.053).CONCLUSIONS:Supplementation with one Brazil nut a day for 8 weeks reduced total cholesterol and glucose levels. Furthermore, our results suggest that rs3877899 might be associated with glucose concentrations and rs7579 with cholesterol concentrations. Therefore, the effect of genetic variations should be considered in future nutritional interventions evaluating the response to Brazil nut supplementation.

Scope The study aims to assess the role of factors assumed to be involved in the transfer of carotenoids from plant matrices to dietary emulsions in the upper digestive tract. Methods and Results Transfer is first measured as a function of time of pure beta-carotene (beta C), lutein (LUT), and lycopene (LYC) to triglyceride (TG) droplets dispersed in water. Then the transfer to TG droplets stabilized with either bovine serum albumin (BSA), phospholipids (PL), or both is measured. Finally, transfer of tomato and spinach puree carotenoids to these emulsions is measured. The maximal transfer efficiency of the pure carotenoids to uncoated emulsions is very efficient, ranging from 59% to 77%. However, it is dramatically impaired, ranging from 0.5% to 31% (p < 0.05), when emulsions are stabilized by the emulsifiers. Conversely, when LUT, and to a less extent beta C, but not LYC, is provided by the vegetable purees, its maximal transfer efficiency is significantly higher for the coated emulsions than for the uncoated one. Conclusions Emulsifiers can dramatically impair the transfer of pure carotenoids to emulsion TG while they can facilitate the transfer of carotenoids from plant matrices. This suggests that specific interactions between plant matrix compounds and emulsifiers can enhance the transfer efficiency of carotenoids.

Food matrix is known to interact with some dietary constituents and microconstituents during digestion. These interactions may potentially affect the metabolism and bioavailability of some compounds, and as a consequence modulate their biological effects. In this context, the aim of this study was to determine the effect of apple food matrix on the bioavailability of flavan-3-ols and on the ability of these compounds to modulate the nutrigenomic response to a high fat challenge in minipigs.Adult male Yucatan minipigs (n = 5) were assigned to a random treatment sequence of high-fat meals non supplemented or supplemented with 250 g of raw apple, 250 g of apple puree or 1.4 g of apple polyphenols extract, with a 7-days washout period between each treatment. Each supplementation provided 155 mg flavan-3-ol monomers. At each treatment period, fasting- and 1h-, 2h-, 3h-postprandial blood samples were collected, and the concentration in flavan-3-ol monomers was measured on hydrolyzed serum, using UPLC-Q-TOF MS. The ability of apple-derived products to modulate the postprandial gene expression profile was assessed and compared in circulating PBMCs collected at 3 h after consumption of the four tested meals using a microarray analysis.Results show that the apple matrix did not affect the kinetic of the postprandial absorption of flavan-3-ol monomers. The total flavan-3-ols concentrations measured at peak were significantly higher in the extract (x1.75), suggesting an impact of the apple matrix on flavan-3-ols absorption. However, no significant difference in total flavanols was observed between raw apple and apple puree.Principal Component Analysis of the microarray data from PBMCs identified three distinct clusters of gene expression patterns: one corresponding to gene expression profiles after the high-fat meal, one for meal supplemented with raw apples or apple puree, and a third cluster for meal supplemented with polyphenol extract. A set of 309 genes was identified as differentially expressed by apple-derived products compared to high-fat meal alone, including 93 modulated with the three apple products. The variations in gene expression were similar for only 75% of the 93 genes, suggesting that the apple matrix affects the nutrigenomic response to flavan-3-ols. A bioinformatics analysis revealed that genes affected by apple-derived products are involved in inflammation and leukocyte transendothelial migration, suggesting a beneficial impact of apple-derived products.In conclusion, these results raise awareness for considering the impact of food matrix on the biological responsiveness of polyphenols in future nutritional studies.

International audience; Scope: To investigate the formation and absorption of lycopene (LYC) metabolites in the human upper gastrointestinal lumen, in the absence and presence of iron. Methods: Healthy males (n = 7) consumed test meals that deliver ≈22 mg LYC + ≈0.3 mg apo-lycopenals from oleoresin without (-FeSO4) and with ferrous sulfate (160 mg, +FeSO4). Subjects were intubated with a naso-gastric/naso-duodenal tube. Digesta, blood plasma, and the triglyceride-rich lipoprotein (TRL) fractions of plasma were analyzed using LC–MS/MS, to measure LYC and apo-lycopenoids. Results: Digesta LYC concentrations increased with time (p = 1.2 × 10−7), decrease with time × iron (p = 1.1 × 10−5), and remain ≈200× higher than apo-lycopenals/lycopenone. Digesta apo-8′-, -10′-, -12′-, -14′-, -15-lycopenal, and apo-13-lycopenone concentrations increased with time (p < 0.01), apo-12′-, -14′-, -15-lycopenal, apo-13-lycopenone increase with iron (p < 0.05), and time × iron decrease apo-8′-, -10′-, -12′-, -14′-, -15-lycopenal, apo-13-lycopenone concentrations (p < 0.01). A 1.9-fold decrease in LYC TRL area-under-the-time-concentration-curve is observed after the test meal +FeSO4 versus the test meal –FeSO4 (p = 0.02). Apo-lycopenals were detected in later TRL fractions, and no apo-lycopenols or apo-lycopenoic acids were observed in any samples. Conclusions: FeSO4 reduces LYC absorption. Apo-lycopenals appear to be absorbed from foods, and not made in significant quantities during digestion.

International audience; Postprandial lipemia, which is one of the main characteristics of the atherogenic dyslipidemia with fasting plasma hypertriglyceridemia, low high-density lipoprotein cholesterol and an increase of small and dense low-density lipoproteins is now considered a causal risk factor for atherosclerotic cardiovascular disease and all-cause mortality. Postprandial lipemia, which is mainly related to the increase in chylomicron production, is frequently elevated in individuals at high cardiovascular risk such as obese or overweight patients, type 2 diabetic patients and subjects with a metabolic syndrome who share an insulin resistant state. It is now well known that chylomicron production and thus postprandial lipemia is highly regulated by many factors such as endogenous factors: circulating factors such as hormones or free fatty acids, genetic variants, circadian rhythms, or exogenous factors: food components, dietary supplements and prescription drugs. In this review, we focused on the effect of nutrients, micronutrients and phytochemicals but also on food structure on chylomicron production and postprandial lipemia.

International audience; Carotenoid intake and tissue levels have been frequently associated with reduced risk of chronic diseases. However, their bioavailability is low and influenced by many dietary related parameters. Divalent mineral cations have been suggested to interfere with carotenoid digestion and to hamper micellarization, a prerequisite for their uptake, via complexation of bile salts and precipitation of fatty acids. In the present investigation, we have evaluated the effects of increasing concentrations of magnesium (0-300 mg L-1), calcium (0-1500 mg L-1), zinc (0-200 mg L-1), and sodium (0-1500 mg L-1; control monovalent cation), on carotenoid bioaccessibility from frequently consumed food items rich in carotenoids (tomato juice, carrot juice, apricot nectar, spinach and field salad), following simulated gastro-intestinal digestion. In addition, physicochemical parameters of digesta (macroviscosity, surface tension), micelle size, and zeta-potential were evaluated. All divalent minerals (DM) reduced bioaccessibility of total carotenoids (P < 0.01), as well as of individual carotenoids. Calcium and magnesium led to reductions of up to 100% at the 2 highest concentrations. Curiously, sodium increased (P < 0.01) carotenoid bioaccessiblity of most investigated matrices. The absolute value of the zeta-potential decreased with increasing concentrations of DM, suggesting a decreased stability of the colloidal digesta dispersion. Viscosity decreased, except for apricot nectar samples, while surface tension increased with DM concentration (P < 0.05). Thus, at physiological ranges, calcium and magnesium could negatively impact carotenoid bioavailability, while for zinc, negative effects were only seen at supplemental concentrations. The potential negative effects of DM on carotenoid bioavailability should be further studied in vivo.

International audience; The aim was to enhance provitamin A carotenoid (proVA CAR) concentrations and bioaccessibility in carrots by manipulating post-harvest factors. To that end, we assessed the effects of Ultraviolet-C light, pulsed light, storage temperature, and storage duration. We also measured CAR bioaccessibility by using an in vitro model. Pulsed light, but not Ultraviolet-C, treatment increased proVA CAR concentrations in the cortex tissue (p

The mechanisms of main tomato carotenes (phytoene, phytofluene, lycopene and β-carotene) intestinal absorption are still only partly understood. We thus compared carotene bioavailability in mice after gavage with carotene-rich oil-in-water emulsions. We also determined each carotene absorption profile along the duodenal-ileal axis of the intestine to identify their respective absorption sites and compared these profiles with the gene expression sites of their identified transporters, i.e. SR-BI and CD36. Our data show that phytofluene presented a significantly higher bioavailability compared to lycopene and β-carotene (areas under the curve of 0.76 ± 0.09 vs. 0.30 ± 0.05, 0.09 ± 0.05 and 0.08 ± 0.01 μmol/L·h for phytofluene, phytoene, lycopene and β-carotene, respectively). β-Carotene was mostly converted in the proximal and median intestine. Phytoene and phytofluene accumulation tended to be more important in the distal intestine, which did not correlate with the proximal expression of both Scarb1 and CD36. Overall, these results highlight the high bioavailability of phytofluene. Junta de Andalucía CAROTINCO-P12-AGR-1287

Scope: Absorption mechanisms of phytoene (PT) and phytofluene (PTF) are poorly known. The main objectives of the study are to measure their micellization and intestinal cell uptake efficiencies and to compare them to those of commonly consumed carotenoids. Other objectives are to assess the involvement of protein(s) in their cellular uptake and whether they compete with other carotenoids for micellization and cellular uptake. Methods and results: Tomato-extract-purified PT and PTF, mainly present as cis-isomers, are much better incorporated in synthetic mixed micelles than pure all-trans lycopene. PT impairs lycopene micellization (−56%, P < 0.05) while PT and PTF do not significantly affect the micellization of other carotenoids, and vice versa. At low concentration, Caco-2 PTF uptake is higher (P < 0.05) than that of PT and lycopene (29%, 21%, and not detectable). SR-BI, but not CD36 neither NPC1L1, is involved in PT and PTF uptake. PT and PTF impair (p < 0.05) β-carotene uptake (−13 and −22%, respectively). Conclusions: The high bioaccessibility of PT and PTF can be partly explained by their high micellization efficiency, which is likely due to their natural cis isomerization and/or to their high molecular flexibility. SR-BI is involved in their cellular uptake, which can explain competitions with other carotenoids. Junta de Andalucía CAROTINCO-P12-AGR-1287

“preprint posted with permission from the Annual Review of Nutrition,2019, 38, © by Annual Reviews, http://www.annualreviews.org.”; International audience; Recent 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.

International audience; Cholecalciferol (D-3) and retinyl palmitate (RP) are the two main fat-soluble vitamins found in foods from animal origin. It is assumed that they are solubilized in mixed micelles prior to their uptake by intestinal cells, but only scarce data are available on the relative efficiency of this process and the molecular interactions that govern it. The extent of solubilization of D-3 and RP in micelles composed of lipids and sodium taurocholate (NaTC) was determined. Then, the molecular interactions between components were analyzed by surface tension and surface pressure measurements. The mixture of lipids and NaTC allowed formation of micelles with higher molecular order, and at lower concentrations than pure NaTC molecules. D-3 solubilization in the aqueous phase rich in mixed micelles was several times higher than that of RP. This was explained by interactions between NaTC or lipids and D-3 thermodynamically more favorable than with RP, and by D-3 self-association.

Background Asymmetric β-apo-carotenoids (nonvitamin A-active metabolites) of provitamin A carotenoids have been observed in humans, but no study has investigated their formation during digestion. Objective The aim of this study was to follow the formation and absorption of asymmetric β-apo-carotenoids during digestion. Design Healthy men were intragastrically and intraduodenally intubated, and randomly assigned to consume a lipid-rich control meal (n = 3) or a lipid-rich test meal containing 20 mg [13C-10]-β-carotene (n = 7). Digesta samples were collected over 5 h, and blood collected over 7 h. The triglyceride-rich lipoprotein (TRL) fractions of plasma were also isolated. Lipophilic extracts of digesta, plasma, and TRL were analyzed via a high-performance liquid chromatography-tandem mass spectrometry method developed to identify [13C]-labeled β-apo-carotenals/carotenone, [13C]-β-apo-carotenols, and [13C]-β-apo-carotenoic acids. Results Relative to [13C]-β-carotene, [13C]-β-apo-carotenal levels remained ∼3 orders of magnitude lower throughout digestion (no [13C]-β-apo-carotenols, or [13C]-β-apo-carotenoic acids were observed). A mixed model determined relative influence of digesta type and time on digesta metabolite level. Increasing time significantly increased the model levels of digesta [13C]-β-apo-10',12',14',15-carotenal and [13C]-β-apo-13-carotenone (P

International audience; Although fruits and vegetables are, by far, our main source of carotenoids (CAR), the intracellular localization and the physical state of CAR in plant cells, as well as interactions with some components of these foods, significantly impair the bioavailability of CAR. The bioaccessibility, i.e. the incorporation of CAR into micelles, is indeed modulated by CAR localisation in the different plastids, e.g. chloroplasts, chromoplasts, as well as by their physical state in these plastids, e.g. as crystals or associated with proteins. CAR bioaccessibility can also be impaired by interactions of CAR, or of bile salts that constitute micelles, with some compounds present in vegetable matrices, e.g. fibers and phytosterols. Conversely, it can be improved by triglycerides present in some fruit and vegetables, e.g. avocados or in other foods. Deciphering the molecular mechanisms that explain the effect of fruit and vegetable matrices on CAR bioavailability allows us to suggest dietary recommendations or food processing or culinary methods that aim to improve the bioavailability of these phytochemicals with some well-established health effects.; Alors que les fruits et légumes sont, de loin, notre principale source de caroténoïdes (CAR), la localisation intracellulaire et l’état physique des CAR dans les cellules végétales, ainsi que des interactions avec certains composants de ces aliments, affectent significativement la biodisponibilité des CAR. La bioaccessibilité (i.e. l’incorporation dans les micelles) est en effet affectée par la localisation des CAR dans les différents plastides présents dans les cellules végétales, e.g. chloroplastes, chromoplastes, et par l’état physique des CAR dans ces plastides, e.g. sous forme crystalline ou associés à des protéines. La bioaccessibilité des CAR peut par ailleurs être diminuée par l’interaction des CAR ou des sels biliaires des micelles, avec certaines molécules présentes dans les matrices végétales, e.g. fibres et phytostérols. Elle peut par contre être augmentée par les triglycérides présents dans certains fruits et légumes, e.g. avocats, ou dans d’autres aliments. La compréhension des mécanismes moléculaires qui expliquent les effets des matrices végétales sur la biodisponibilité des CAR permet de proposer des recommandations nutritionnelles et/ou des traitements technologiques ou culinaires visant à optimiser la biodisponibilité de ces phytomicronutriments à effets santé.

EgeUn###, beta-Carotene intake and tissue/blood concentrations have been associated with reduced incidence of several chronic diseases. Further bioactive carotenoid-metabolites can modulate the expression of specific genes mainly via the nuclear hormone receptors: retinoic acid receptor- and retinoid X receptor-mediated signalling. To better understand the metabolic conversion of beta-carotene, inter-individual differences regarding beta-carotene bioavailability and bioactivity are key steps that determine its further metabolism and bioactivation and mediated signalling. Major carotenoid metabolites, the retinoids, can be stored as esters or further oxidised and excreted via phase 2 metabolism pathways. In this review, we aim to highlight the major critical control points that determine the fate of beta-carotene in the human body, with a special emphasis on beta-carotene oxygenase 1. The hypothesis that higher dietary beta-carotene intake and serum level results in higher beta-carotene-mediated signalling is partly questioned. Alternative autoregulatory mechanisms in beta-carotene / retinoid-mediated signalling are highlighted to better predict and optimise nutritional strategies involving beta-carotene-related health beneficial mediated effects., Nutr Soc, Scottish Sect, EU-COST action POSITIVE [FA 1403]; EU-COST action EUROCAROTEN [CA 15136], The insights from EU-COST action POSITIVE (FA 1403) and EUROCAROTEN (CA 15136) are much appreciated.

International audience; Recently isolated spore-forming pigmented marine bacteria, Bacillus indicus HU36 and Bacillus firmus GB1 are sources of carotenoids ( fifteen distinct yellow and orange pigments and thirteen distinct pink pigments, respectively). They are glycosides of oxygenated lycopene derivatives (apo-lycopenoids) and are assumed to be more heat- and gastric-stable than common carotenoids. In this study, the oxidation by O2 of the bacterial carotenoids was initiated by free iron (FeII and FeIII) or by heme iron (metmyoglobin) in a mildly acidic aqueous solution mimicking the gastro-intestinal compartment and compared to the oxidation of the common dietary carotenoids β-carotene, lycopene and astaxanthin. Under these conditions, all bacterial carotenoids appear more stable in the presence of heme iron vs. free iron. Carotenoid autoxidation initiated by FeII is relatively fast and likely involves reactive oxygen–iron species derived from FeII and O2. By contrast, the corresponding reaction with FeIII is kinetically blocked by the slow preliminary reduction of FeIII into FeII by the carotenoids. The stability of carotenoids toward autoxidation increases as follows: β-carotene < lycopene < astaxanthin < HU36 and GB1. In particular, bacterial carotenoids react more quickly than reference carotenoids with FeIII, but much more slowly than the reference carotenoids with FeII. This reaction is correlated with the structure of the carotenoids, which can have opposite effects in a micellar system: bacterial carotenoids with electro-attracting terminal groups have a lower reducing capacity than b-carotene and lycopene. However, their polar head favours their location close to the interface of micelles, in closer contact with oxidative species. Kinetic analyses of the ironinduced autoxidation of astaxanthin and HU36 carotenoids has been performed and gives insights in the underlying mechanisms.

International audience; Magnesium may reduce carotenoid bioavailability by forming insoluble complexes with bile salts/fatty acids, inhibiting micelle formation. Here, we investigated whether altering bile/pancreatin concentration influenced potential negative effects of magnesium on carotenoid bioaccessibility. Spinach (4 g) was digested in vitro with added magnesium (0, 200, 400 mg/L) and canola oil/coffee creamer, at varying bile extract (1 or 8 mM) and pancreatin (100 or 990 mg/L) concentrations. Bioaccessibility was determined for β-carotene, lutein, and total carotenoids via HPLC. Additionally, lipolysis, particle size, and zeta potential of the micellar fractions were investigated. Increasing magnesium concentrations negatively affected carotenoid bioaccessibility (p < 0.001), lipolysis, particle size and zeta potential. The impact of magnesium on carotenoid bioaccessibility was modulated mainly by bile concentration, with samples digested with 1 mM of bile being more susceptible to inhibitory effects of magnesium than those digested with 8 mM (p < 0.001). Thus, magnesium was found to potentially interfere with carotenoid bioaccessibility at various physiologically plausible conditions.

This work was supported by an INRA Priority Action of the "Alimentation Humaine" department (2013-2015). Marielle Margier received a doctoral fellowship (2015-2018) from Region PACA in partnership with the Centre Technique de Conservation des Produits Alimentaires (CTCPA, Avignon); Scope: Food matrix is generally believed to alter carotenoid bioavailability, but its effect on xanthophylls is usually limited. This study thus aims to decipher the digestion-absorption process of lutein in the presence or not of a food matrix.Methods: Lutein transfer to gastric-like lipid droplets or artificial mixed micelles was assessed when lutein was added to test meals either as a pure molecule ((all-E)-lutein) or in canned spinach ((Z) + (all-E)-lutein). The obtained mixed micelles were delivered to Caco-2 cells to evaluate lutein uptake. Finally postprandial plasma lutein responses were compared in minipigs after the two test meals.Results: Lutein transfer to gastric-like lipid droplets and to mixed micelles was higher when lutein was added in spinach than when it was added as pure lutein (+614% and +147%, respectively, p < 0.05). Conversely, lutein uptake was less effective when micellar lutein was from a meal containing spinach than from a meal containing its pure form (-55%, p < 0.05). In minipigs, postprandial lutein response was delayed with spinach but not significantly different after the two test meals.Conclusion: Opposite effects at the micellarization and intestinal cell uptake steps explain the lack of effect of spinach matrix on lutein bioavailability.

Purpose of review To provide an update on the genetic factors recently associated with the interindividual variability of tomato carotenoid bioavailability. Recent findings Several clinical studies have demonstrated that the main carotenoids found in tomatoes (lycopene, phytoene, phytofluene, β-carotene, lutein) all display relatively large interindividual variabilities of their bioavailability, with coefficients of variations more than 70%. The bioavailability of the parent molecules, and the blood/tissue appearance of their metabolites, is modulated by numerous proteins, involved in intestinal absorption and metabolism, blood lipoprotein transport or tissue uptake. Several single nucleotide polymorphisms (SNPs) have been associated with the interindividual variability of lycopene, lutein and β-carotene bioavailability, with six genes consistently shared between the three carotenoids, and in particular one SNP in ELOVL fatty acid elongase 2. The effects of the genetic variants taken separately are relatively low, that is each variant is usually associated with only a few percentage of the variability but multivariate analyses suggest that the additive effect of several genetic variants can explain a significant fraction of tomato carotenoid bioavailability. Summary Additional studies are needed to improve our knowledge of the genetic determinants of tomato carotenoid bioavailability but progress in this field could one day allow nutritionists to provide more personalized dietary recommendations.