Etude de l’impact de l’environnement et de la génétique sur la qualité nutritionnelle du colza par une approche métabolomique

Rapeseed (Brassica napus) is the first oleaginous crop in France. It is cultivated for the abundance of its seeds in lipids, proteins as well as for its richness in secondary metabolites that can modulate the health of the consumer. Thus different actions have been implemented by food and feed industries to reduce the rate of anti-nutritional metabolites. Conversely few are devoted to the exploitation of health promoting molecules. One of the ways is to identify the conditions of culture in interaction with the genotypes to generate seeds of optimal nutritional quality. This project focuses on the exploration of the polar fraction of the metabolome of several commercial varieties of Brassica napus and its repercussions on health. During this project different varieties of rapeseed, grown in different regions of France were harvested during 2015 then 2016, and their quality assessed by a metabolomic approach. In general, the results showed that some varieties are resilient to the environment such as Pamela, Bonanza, ES-Mambo, Alicante and PT256. Others, on the other hand, have shown themselves to be more sensitive to the environment, which suggests the manipulation of this factor to obtain seeds of the desired quality. The contrast regarding the secondary metabolites observed between varieties reflects the influence of the interaction between the genetic background and the environment. We chose two types of seeds that had the most highlighted contrast regarding the quality of their secondary metabolites, in order to validate whether qualitative differences of this kind can be manifested by a different biological response in the consumer. This response was evaluated on a preclinical model ob/ob mouse by a multi-omic approach, and compared to a reference extract from Brassica oleracea (Broccoli), marketed for its health benefits. The results showed that the "omic" biological response measured in the intestine, liver and plasma showed a strong proximity between one of the rapeseed extract (ES-Mambo) and the reference extract (Broccoli). We believe that this results occur from the presence of common bioactive compounds between the two plants (rapeseed and broccoli), which we have been able to identify some of them (polyphenols and glucosinolates). The integrated biological response indicated that both extracts beneficially regulated certain metabolic processes, lipid metabolism, immune function, and nucleoside and lipid metabolism of the microbiota. Moreover, there appeared to be a vast coordination of biological phenomena between the microbiota and the host. Thus, our broad spectrum bioassay indicates that the ES-Mambo variety has properties similar to the Broccoli extract, marketed for its health benefits. These results allow to consider a valorization of the extract coming from the variety ES-Mambo. In conclusion, the metabolomic approach used in this study proved to be a powerful approach to identify the sources of natural variations brought by the environment and the genotype that impact the nutritional quality of the rapeseed. In addition, our holistic, multi-scale approach has made it possible to estimate the real health impact of phytochemical extracts that have never been evaluated before. The approach demonstrated that the culture conditions and the genotype of rapeseed that modified their bioactive content induced a differential biological response in the consumer.Le colza (Brassica napus) est la première espèce oléagineuse en France. Elle est cultivée pour la richesse de ses graines en lipides et protéines. Elle possède aussi des métabolites secondaires bioactifs pouvant moduler la santé du consommateur. Ainsi différentes actions ont été mises en place par les industries agroalimentaires pour réduire le taux de métabolites antinutritionnels. A l’inverse peu sont consacrés à l’exploitation des métabolites favorables à la santé. L’une des pistes est d’identifier les conditions de culture en interaction avec les génotypes pour générer des graines de qualité nutritionnelle optimale. Cee projet s’intéresse à l’exploration de la fraction polaire du métabolome de graines issues de plusieurs variétés commerciales de Brassica napus, et à son retentissement sur la santé. Au cours de ce projet différentes variétés de colza, ont été cultivées dans différentes régions de France et récoltées en 2015 et 2016 et leur qualité évaluée par une approche métabolomique. D’une manière générale, les résultats ont montré que certaines variétés sont résilientes à l’environnement comme les variétés Pamela, Bonanza, ES-Mambo, Alicante et PT256. D’autres au contraire se sont montrées plus sensibles à l’environnement, ce qui laisse présager la manipulation de ce facteur pour obtenir des graines de qualité voulue. Le contraste en métabolites secondaires entre les variétés reflète l’influence de l’interaction entre le fond génétique et l’environnement. Nous avons choisi deux types de graines qui présentaient le contraste le plus marquée pour la qualité de leurs métabolites secondaires, afin de valider si des différences qualitatives de cet ordre peuvent manifester par une réponse biologique différente chez le consommateur. Cette réponse a été évaluée sur un modèle préclinique de souris ob/ob par une approche multi-omique, et comparée à celle d’un extrait de référence issu de Brassica oleracea (Brocoli) commercialisé pour ces vertus santé. Les résultats ont montré que la réponse biologique « omique » mesurée dans l’intestin, le foie et le plasma présentait une forte proximité entre l’un des extrait de colza (ES-Mambo) avec l’extrait de référence (Brocoli). Nous pensons que cela résulte de la présence de composés bioactifs communs et minoritaires entre les deux plantes et dont nous avons pu identifier la nature de certains (polyphénols et glucosinolates). La réponse biologique intégrée indiquait que les deux extraits régulaient de façon bénéfique certains processus métaboliques, le métabolisme des lipides, la fonction immunitaire, ainsi que les métabolismes des nucléosides et lipidiques du microbiote. Il apparaissait d’ailleurs une coordination vaste des phénomènes biologiques entre le microbiote et l’hôte. Notre évaluation biologique à large spectre indique ainsi que la variété ES-Mambo possède des propriétés analogues à l’extrait de Brocoli de référence commercialisé pour ces vertus santés. Ces résultats permettent de considérer une valorisation de l’extrait provenant de la variété ES-Mambo. En conclusion, l’approche métabolomique utilisée dans cette étude s’est révélée comme une approche puissante pour identifier les sources de variations naturelles apportées par l'environnement et le génotype qui impactent la qualité nutritionnelle de la graine de colza. De plus, notre approche holistique multi-échelles a permis d’estimer l'impact réel sur la santé d'extraits phytochimiques, non évalués auparavant. L’approche a démontré que les conditions de culture et le génotype du colza ayant modifié leur contenu bioactif induisaient une réponse biologique différentielle chez le consommateur

The study of the impact of environment and genetics on the nutritional quality of rapeseed by a metabolomic approach

Le colza (Brassica napus) est cultivée pour la richesse de ses graines en lipides et protéines. Cette plante possède aussi des métabolites secondaires bioactifs pouvant moduler la santé du consommateur. Ainsi différentes actions ont été mises en place par les industries agroalimentaires pour réduire le taux de métabolites antinutritionnels. A l’inverse peu sont consacrés à l’exploitation des métabolites favorables à la santé. L’une des pistes est d’identifier les conditions de culture en interaction avec les génotypes pour générer des graines de qualité nutritionnelle optimale. D’une manière générale, les résultats ont montré que certaines variétés sont résilientes à l’environnement. D’autres au contraire se sont montrées plus sensibles. L'impact des IGEC observé a été évaluée sur un modèle préclinique de souris ob/ob par une approche multi-omique, et comparée à celle d’un extrait de référence issu de Brassica oleracea (Brocoli) commercialisé pour ces vertus santé. Les résultats ont montré que la réponse biologique « omique » mesurée dans l’intestin, le foie et le plasma présentait une forte proximité entre l’un des extraits de colza (ES-Mambo) avec l’extrait de référence (Brocoli). Nous pensons que cela résulte de la présence de composés bioactifs communs et minoritaires entre les deux plantes et dont nous avons pu identifier la nature de certains (composés phénoliques et glucosinolates). L’approche métabolomique a démontré que les conditions de culture et le génotype du colza ayant modifié leur contenu bioactif induisaient une réponse biologique différentielle chez le consommateur. Cette preuve de concept pourrait s’appliquer à d’autres plantes de grande consommation.Rapeseed (Brassica napus) is the first oleaginous crop in France. It is cultivated for the abundance of its seeds in lipids, proteins as wellas for its richness in secondary metabolites that can modulate the health of the consumer. For instance, different actions have beenimplemented by food and feed industries to reduce the rate of anti-nutritional metabolites. Conversely few are devoted to theexploitation of health promoting molecules. A strategy is to identify the genotype x environment x agronomic management interactions(GEAI) to generate seeds of optimal nutritional quality.The results showed that some varieties are resilient to the environment. On the other hand, others appeared more sensitive. The environment and genetic impact was evaluated on a preclinical model ob/ob mouse by a multi-omic approach, and compared to a reference extract from Brassica oleracea (Broccoli), marketed for its health benefits. The results showed that the "omic" biological response measured in the intestine, liver and plasma showed a strong proximity between one of the rapeseed extract (ES-Mambo) and the reference extract (Broccoli). We believe that these results occured from the presence of common bioactive compounds between the two plants (rapeseed and broccoli), that some of them were identified (phenolic compounds and glucosinolates). The metabolomic approach was efficient to estimate the health impact of phytochemical extracts that have never been evaluated before. We demonstrated that the GEAI of rapeseed that modified their bioactive contents induced a differential biological response in the consumer. This proof of concept study could be applied to other food plant products

The Effects of Doxorubicin-based Chemotherapy and Omega-3 Supplementation on Mouse Brain Lipids

Chemotherapy-induced cognitive impairment affects ~30% of breast cancer survivors, but the effects on how chemotherapy impacts brain lipids, and how omega-3 polyunsaturated fatty acid supplementation may confer protection, is unknown. Ovariectomized mice were randomized to two rounds of injections of doxorubicin + cyclophosphamide or vehicle after consuming a diet supplemented with 2% or 0% EPA+DHA, and sacrificed 4, 7, and 14 days after the last injection (study 1, n = 120) or sacrificed 10 days after the last injection (study 2, n = 40). Study 1 whole brain samples were extracted and analyzed by UHPLC-MS/MS to quantify specialized pro-resolving mediators (SPMs). Lipidomics analyses were performed on hippocampal extracts from study 2 to determine changes in the brain lipidome. Study 1 results: only resolvin D1 was present in all samples, but no differences in concentration were observed (P \u3e 0.05). Study 2 results: chemotherapy was positively correlated with omega-9 fatty acids, and EPA+DHA supplementation helped to maintain levels of plasmalogens. No statistically significant chemotherapy*diet effect was observed. Results demonstrate a limited role of SPMs in the brain post-chemotherapy, but a significant alteration of hippocampal lipids previously associated with other models of cognitive impairment (i.e., Alzheimer’s and Parkinson’s disease)

The Effects of Doxorubicin-based Chemotherapy and Omega-3 Supplementation on Mouse Brain Lipids

Chemotherapy-induced cognitive impairment affects ~30% of breast cancer survivors, but the effects on how chemotherapy impacts brain lipids, and how omega-3 polyunsaturated fatty acid supplementation may confer protection, is unknown. Ovariectomized mice were randomized to two rounds of injections of doxorubicin + cyclophosphamide or vehicle after consuming a diet supplemented with 2% or 0% EPA+DHA, and sacrificed 4, 7, and 14 days after the last injection (study 1, n = 120) or sacrificed 10 days after the last injection (study 2, n = 40). Study 1 whole brain samples were extracted and analyzed by UHPLC-MS/MS to quantify specialized pro-resolving mediators (SPMs). Lipidomics analyses were performed on hippocampal extracts from study 2 to determine changes in the brain lipidome. Study 1 results: only resolvin D1 was present in all samples, but no differences in concentration were observed (P > 0.05). Study 2 results: chemotherapy was positively correlated with omega-9 fatty acids, and EPA+DHA supplementation helped to maintain levels of plasmalogens. No statistically significant chemotherapy*diet effect was observed. Results demonstrate a limited role of SPMs in the brain post-chemotherapy, but a significant alteration of hippocampal lipids previously associated with other models of cognitive impairment (i.e., Alzheimer’s and Parkinson’s disease)

Analyse métabolomique LC-HRMS de foies de ratons exposés in-utero au Bisphénol A

Analyse métabolomique LC-HRMS de foies de ratons exposés in-utero au Bisphénol A. 10. Journées scientifiques du Réseau Francophone de Métabolomique et Fluxomique RFMF 201

Assessment of the effects of repeated doses of potassium iodide intake during pregnancy on male and female rat offspring using metabolomics and lipidomics

International audiencePreparedness for nuclear accident responsiveness includes interventions to protect pregnancies against prolonged exposure to radioactive iodine. The aim of this study was to investigate a new design consisting of repeated administration of potassium iodide (KI, 1 mg/kg) for 8 days in late pregnancy gestational day 9–16 (GD9–GD16) in rats. The later-life effects of this early-life iodine thyroid blocking (ITB) strategy were assessed in offspring two months afterbirth. Functional behavioral tests including forced swimming test (FST) and rotarod test (RRT) in rats of both genders showed lower FST performance in KI-treated females and lower RRT performance in KI-treated male pups. This performance decline was associated with metabolic disruptions in cortex involving amino acid metabolism, tyrosine metabolism, as well as docosahexaenoic acid (DHA) lipids and signaling lipids in males and females. Beyond these behavior-associated metabolic changes, a portion of the captured metabolome (17–25%) and lipidome (3.7–7.35%) remained sensitive to in utero KI prophylactic treatment in both cortex and plasma of post-weaning rats, with some gender-related variance. Only part of these disruptions was attributed to lower levels of TSH and T4 (males only). The KI-induced metabolic shifts involved a broad spectrum of functions encompassing metabolic and cell homeostasis and cell signaling functions. Irrespective Regardless of gender and tissues, the predominant effects of KI affected neurotransmitters, amino acid metabolism, and omega-3 DHA metabolism. Taken together, data demonstrated that repeated daily KI administration at 1 mg/kg/day for 8 days during late pregnancy failed to protect the mother-fetus against nuclear accident radiation

The impact of genetics and environment on the polar fraction metabolome of commercial Brassica napus seeds: a multi-site study

International audienceThis study was designed to elucidate the biological variation in expression of many metabolites due to environment, genotype, or both, and to investigate the potential utility of metabolomics to supplement compositional analysis for the design of a new resilient cultivar of Brassica napus that can be steady in phytochemicals in different regions in France. Eight rapeseed varieties, grown in eight regions of France, were compared using a non-targeted metabolomics approach. The statistical analysis highlighted the distance and closeness between the samples in terms of both genotypes and geographical regions. A major environmental impact was observed on the polar metabolome, with different trends, depending on the varieties. Some varieties were very sensitive to the environment, while others were quite resilient. The identified secondary metabolites were mapped into the KEGG pathway database to reveal the most sensitive target proteins susceptible to environmental influences. A glucosyl-transferase encoded by the UGT84A1 gene involved in the biosynthesis of phenylpropanoid was identified. This protein could be rate limiting/promoting in this pathway depending on environmental conditions. The metabolomics approach used in this study demonstrated its efficiency to characterize the environmental influence on various cultivars of Brassica napus seeds and may help identify targets for crop improvement

Effect of genetic and environment on the polar fraction metabolome of commercial Brassica napus seeds: a multisite study

International audienc

The Brassica napus (oilseed rape) seeds bioactive health effects are modulated by agronomical traits as assessed by a multi-scale omics approach in the metabolically impaired ob-mouse

International audienceBeside oil, oilseed rape (Brassica napus) seeds contains nutritional bioactives such as polyphenols and glucosinolates. However, to date their nutritional properties have been overlooked in the new "double zero" breeds. Seed alcoholic extracts from two B. napus cultivars most contrasting in their phytochemical contents as measured by mass-spectrometry were given to ob-mice. Biological outcomes including clinical metrics, gut and plasma metabolomes, liver transcriptome and metabolome were compared to ob-mice given a similar broccoli extract (Brassica oleracea). One B. napus extract induced a reduction of the oxidative stress indicated by the decrease of plasma isoprostanoids. This was associated to the regulation of the antioxidant stress defense Nrf2 pathway, to 'omic' oxidative stress functions, metabolic and cell process regulations, and the metabolomics microbiota profile. Extracts of B. napus seeds demonstrated health effects that may be improved by selecting appropriate agronomical traits, highlighting the potential benefits of better utilizing agronomy for improved human and animal nutritio