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International audience; The postnatal period is characterized by rapid growth and development. Lipids, especially long-chain polyunsaturated fatty acids (LC-PUFA) such as docosahexaenoic (DHA) and arachidonic (ARA) acids, play an essential role during this period. The main objective of infant formulas is to be biomimetic of the “golden standard” i.e. breast milk, both in terms of composition and structure, thus offering the best possible alternative to breastfeeding when it has failed and/or is not possible. In this context, European regulations have evolved and now require DHA supplementation of formulas. Formulas are also fortified with ARA, another PUFA essential for child development, although there is no requirement for a minimum content. Their high degree of unsaturation makes these fatty acids particularly sensitive to lipid oxidation, making their inclusion in infant formulas more difficult. The objective of this review is therefore to provide a state of the art on the various key parameters that allow better control of LC-PUFA supplementation in infant formulas.; La période postnatale est caractérisée par une croissance et un développement rapide. Les lipides, et plus particulièrement les acides gras polyinsaturés à longues chaînes (AGPI-LC), tels que les acides docosahexaénoïque (DHA) et arachidonique (ARA), jouent un rôle essentiel durant cette période. L’objectif principal des formules infantiles est d’être biomimétique de « l’étalon d’or » : le lait maternel, aussi bien en termes de composition que de structure, pour ainsi offrir la meilleure alternative possible à l’allaitement lorsqu’il a échoué et/ou n’est pas possible. Dans ce contexte, la réglementation européenne a évolué et impose désormais la supplémentation des formules en DHA. Elles sont également fortifiées en ARA, autre AGPI indispensable pour le développement de l’enfant, bien qu’aucune obligation ne soit établie quant à sa teneur minimale. Leur important degré d’insaturation rend ces acides gras particulièrement sensibles à l’oxydation lipidique, complexifiant ainsi leur introduction dans les formules infantiles. L’objectif de cette revue est donc de faire un état de l’art sur les différents paramètres clés permettant de mieux maîtriser la supplémentation des formules infantiles en AGPI-LC.

International audience; Oil bodies (OB), the form of triacylglycerol storage in seeds, are interesting natural assemblies for nutritional applications. In walnuts, OB contain an important amount of polyunsaturated fatty acids that could be interesting food ingredients but may be prone to oxidation. The oxidative and interfacial behavior of walnut OB, either minimally-processed or after processing, were compared with processed complex walnut juice. The good oxidative stability of minimally-processed OB over 10 days (PV ≤ 8.4 meq O2/kg, TBARS = 1.4 mmol eq MDA/kg) and of processed walnut complex matrixes over 20 days (PV ≤ 4.8 meq O2/kg, TBARS = 1.4 mmol eq MDA/kg) was evidenced. In comparison, processing of OB promoted their oxidation. The interfacial studies led to the proposition of a new model of adsorption for minimally-processed OB that will be useful to design functional emulsion or foam in which OB act as emulsifiers.

International audience; Guinea fowl production is increasing in developing countries and has a crucial role in the fight against poverty. However, the feed cost is very high, especially the soya bean meal cost, and farmers cannot afford to buy commercial feed. Consequently, animals do not receive feed adapted to their nutritional needs and they exhibit poor performance. The aim of this paper is to partially substitute soya bean meal by local by-products, discarded, in abundant supply and not used in human nutrition. French Galor guinea fowl (Numida meleagris) and local African guinea fowl (150 birds per breed) were reared for 16 weeks and fed the same starter diet for the initial 4 weeks. From 4 weeks of age, experimental birds from each breed were randomly assigned to three grower isoproteic and isolipidic dietary treatments, each containing five replications (floor pens); each replication included 10 birds of the same breed. The guinea fowl of each breed were fed either control grower diet using soya bean meal as the protein supplement GS, or trial grower diet GN (soya bean meal supplement partially substituted by 15% cashew nut (Anacardium occidentale) meal) or trial grower diet GH (soya bean meal supplement partially substituted by 15% hevea seed (Hevea brasiliensis) meal). The results indicated that hevea seed meal contained a high content of n-3 polyunsaturated fatty acids (PUFAs) (21.2% of total fatty acids (FAs)). The use of hevea seed meal in guinea fowl grower diet was found to exert no adverse effect on growth performance and carcass yield. However, the use of cashew nut meal led to negative effects on performance like daily weight gain and feed conversion ratio. Therefore, cashew nut meal cannot be considered as a suitable partial substitute for soya bean meal in diets. The use of hevea seed meal led to a very low abdominal fat proportion and low blood triglyceride and cholesterol content. Additionally, inclusion of dietary hevea seed meal resulted in guinea fowl meat enriched in PUFAs, especially n-3 FAs, thereby significantly improving the nutritional value.

© 2019 Morello, Pérez-Berezo, Boisseau, Baranek, Guillon, Bréa, Lanotte, Carpena, Pietrancosta, Hervé, Ramphal, Cenac and Si-Tahar., Pseudomonas aeruginosa is an opportunistic bacteria and a major cause of nosocomial pneumonia. P. aeruginosa has many virulence factors contributing to its ability to colonize the host. LoxA is a lipoxygenase enzyme secreted by P. aeruginosa that oxidizes polyunsaturated fatty acids. Based on previous in vitro biochemical studies, several biological roles of LoxA have been hypothesized, including interference of the host lipid signaling, and modulation of bacterial invasion properties. However, the contribution of LoxA to P. aeruginosa lung pathogenesis per se remained unclear. In this study, we used complementary in vitro and in vivo approaches, clinical strains of P. aeruginosa as well as lipidomics technology to investigate the role of LoxA in lung infection. We found that several P. aeruginosa clinical isolates express LoxA. When secreted in the lungs, LoxA processes a wide range of host polyunsaturated fatty acids, which further results in the production of bioactive lipid mediators (including lipoxin A4). LoxA also inhibits the expression of major chemokines (e.g., MIPs and KC) and the recruitment of key leukocytes. Remarkably, LoxA promotes P. aeruginosa persistence in lungs tissues. Hence, our study suggests that LoxA-dependent interference of the host lipid pathways may contribute to P. aeruginosa lung pathogenesis., This work was funded by the “INSERM” and “Université de Tours” endowments as well as with the support of the French Cystic Fibrosis Foundation “Vaincre la Mucoviscidose” (Grant Number RF20140501103) and FeRI (Fédération de Recherche en Infectiologie – Centre Val de Loire Region, Grant Number A03-2016).

The many functions of astrocytes, such as glutamate recycling and morphological plasticity, enable them to stabilize synapses environment and protect neurons. Little is known about how they adapt to glucocorticoid-induced stress, and even less about the influence of dietary factors. We previously showed that omega-3 polyunsaturated fatty acids (ω3PUFA), dietary fats which alleviate stress responses, influence the way astroglia regulate glutamatergic synapses. We have explored the role of docosahexaenoic acid (DHA), the main ω3PUFA, in the astroglial responses to corticosterone, the main stress hormone in rodents to determine whether ω3PUFA help astrocytes resist stress. Cultured rat astrocytes were enriched in DHA or arachidonic acid (AA, the main ω6PUFA) and given 100 nM corticosterone for several days. Corticosterone stimulated astrocyte glutamate recycling by increasing glutamate uptake and glutamine synthetase (GS), and altered the astrocyte cytoskeleton. DHA-enriched astrocytes no longer responded to the action of corticosterone on glutamate uptake, had decreased GS, and the cytoskeletal effect of corticosterone was delayed, while AA-enriched cells were unaffected. The DHA-dependent anti-corticosterone effect was related to fewer glucocorticoid receptors, while corticosterone increased DHA incorporation into astrocyte membranes. Thus, DHA helps astrocytes resist the influence of corticosterone, so perhaps promoting a sustainable response by the stressed brain. We show that corticosterone increases the glutamate recycling capacity of rat cortical astrocytes in culture, and alters their morphology, which may be detrimental in the long term. Increasing the membrane incorporation of docosahexaenoic acid (DHA), the main omega-3 in brain, reduces the amount of glucocorticoid receptors (GR) and prevents the effects of corticosterone. This may help the astrocytes maintain a functional phenotype in chronic stress situations.

By their autotrophic nature and their molecular richness, microalgae are serious assets in the context of current environmental and societal challenges. Some species produce both omega-3 long chain polyunsaturated fatty acids (PUFAs) and xanthophylls, two molecular families widely studied for their bioactivities in the fields of nutrition and cosmetics. Whereas most studies separately deal with the two families, synergies could be exploited with extracts containing both PUFAs and xanthophylls. The purpose of our work was to determine cost effective and eco-friendly parameters for their co-extraction. The effect of several parameters (solvent, solvent/biomass ratio, temperature, duration) were studied, using two microalgal species, the non-calcifying Haptophyta Tisochrysis lutea, and the diatom Phaeodactylum tricornutum, that presents a silicified frustule. Analyses of PUFAs and fucoxanthin (Fx), the main xanthophyll, allowed to compare kinetics and extraction yields between experimental protocols. Co-extraction yields achieved using 96% ethanol as solvent were 100% for Fx and docosahexaenoic acid (DHA) in one hour from T. lutea biomass, and respectively 95% and 89% for Fx and eicosapentaenoic acid (EPA) in eight hours from P. tricornutum. These conditions are compatible with industrial applications.

Open access original paper Source : 10th EPR Workshop on Applications of EPR in Biology and Medicine, 2016 in Krakow, POLAND.; International audience; The mammalian retina contains a high level of polyunsaturated fatty acids, including docosahexaenoic acid (22:6) (DHA), which are highly susceptible to oxidation. It has been shown that one of the products of DHA oxidation-carboxyethylpyrrole (CEP), generated in situ, causes modifications of retinal proteins and induces inflammation response in the outer retina. These contributing factors may play a role in the development of age-related macular degeneration (AMD). It is also possible that some of the lipid oxidation products are photoreactive, and upon irradiation with blue light may generate reactive oxygen species. Therefore, in this work we analysed oxidation-induced changes in photoreactivity of lipids extracted from bovine neural retinas. Lipid composition of bovine neural retinas closely resembles that of human retinas making the bovine tissue a convenient model for studying the photoreactivity and potential phototoxicity of oxidized human retinal lipids. Lipid composition of bovine neural retinas Folch' extracts (BRex) was determined by gas chromatography (GC) and liquid chromatography coupled to an electrospray ionization source-mass spectrometer (LC-ESI-MS) analysis. Liposomes prepared from BRex, equilibrated with air, were oxidized in the dark at 37 A degrees C for up to 400 h. The photoreactivity of BRex at different stages of oxidation was studied by EPR-oximetry and EPR-spin trapping. Photogeneration of singlet oxygen (O-1(2), (1)Delta(g)) by BRex was measured using time-resolved detection of the characteristic phosphorescence at 1270 nm. To establish contribution of lipid components to the analysed photoreactivity of Folch' extract of bovine retinas, a mixture of selected synthetic lipids in percent by weight (w/w %) ratio resembling that of the BRex has been also studied. Folch's extraction of bovine neural retinas was very susceptible to oxidation despite the presence of powerful endogenous antioxidants such as alpha-tocopherol and zeaxanthin. Non-oxidized and oxidized BRex photogenerated singlet oxygen with moderate quantum yield. Blue-light induced generation of superoxide anion by Folch' extract of bovine neural retinas strongly depended on the oxidation time. The observed photoreactivity of the studied extract gradually increased during its in vitro oxidation.

The 178 microarrays are MIAME compliant and available in Gene Expression Omnibus (GEO) through GEO Series accession number GSE104042 andplatform number GPL19630.; International audience; Background: Because the cost of cereals is unstable and represents a large part of production charges for meattype chicken, there is an urge to formulate alternative diets from more cost-effective feedstuff. We have recently shown that meat-type chicken source is prone to adapt to dietary starch substitution with fat and fiber. The aim of this study was to better understand the molecular mechanisms of this adaptation to changes in dietary energy sources through the fine characterization of transcriptomic changes occurring in three major metabolic tissues – liver, adipose tissue and muscle – as well as in circulating blood cells.Results: We revealed the fine-tuned regulation of many hepatic genes encoding key enzymes driving glycogenesis and de novo fatty acid synthesis pathways and of some genes participating in oxidation. Among the genes expressed upon consumption of a high-fat, high-fiber diet, we highlighted CPT1A, which encodes a key enzyme in the regulation of fatty acid oxidation. Conversely, the repression of lipogenic genes by the high-fat diet was clearly associated with the downregulation of SREBF1 transcripts but was not associated with the transcript regulation of MLXIPL and NR1H3, which are both transcription factors. This result suggests a pivotal role for SREBF1 in lipogenesis regulation in response to a decrease in dietary starch and an increase in dietary PUFA. Other prospective regulators of de novo hepatic lipogenesis were suggested, such as PPARD, JUN, TADA2A and KAT2B, the last two genes belonging to the lysine acetyl transferase (KAT) complex family regulating histone and non-histone protein acetylation. Hepatic glycogenic genes were also down-regulated in chickens fed a high-fat, high-fiber diet compared to those in chickens fed a starch-based diet. No significant dietary-associated variations in gene expression profiles was observed in the other studied tissues, suggesting that the liver mainly contributed to the adaptation of birds to changes in energy source and nutrients in their diets, at least at the transcriptional level. Moreover, we showed that PUFA deposition observed in the different tissues may not rely on transcriptional changes.Conclusion: We showed the major role of the liver, at the gene expression level, in the adaptive response of chicken to dietary starch substitution with fat and fiber.

Energy-dense, yet nutritionally poor food is a high-risk factor for mental health disorders. This is of particular concern during adolescence, a period often associated with increased consumption of low nutritional content food and higher prevalence of mental health disorders. Indeed, there is an urgent need to understand the mechanisms linking unhealthy diet and mental disorders. Deficiency in n-3 polyunsaturated fatty acids (PUFAs) is a hallmark of poor nutrition and mood disorders. Here, we developed a mouse model of n-3 PUFA deficiency lasting from adolescence into adulthood. Starting nutritional deficits in dietary n-3 PUFAs during adolescence decreased n-3 PUFAs in both medial prefrontal cortex (mPFC) and nucleus accumbens, increased anxiety-like behavior, and decreased cognitive function in adulthood. Importantly, we discovered that endocannabinoid/mGlu5-mediated LTD in the mPFC and accumbens was abolished in adult n-3-deficient mice. Additionally, mPFC NMDAR-dependent LTP was also lacking in the n-3-deficient group. Pharmacological enhancement of the mGlu5/eCB signaling complex, by positive allosteric modulation of mGlu5 or inhibition of endocannabinoid 2-arachidonylglycerol degradation, fully restored synaptic plasticity and normalized emotional and cognitive behaviors in malnourished adult mice. Our data support a model where nutrition is a key environmental factor influencing the working synaptic range into adulthood, long after the end of the perinatal period. These findings have important implications for the identification of nutritional risk factors for disease and design of new treatments for the behavioral deficits associated with nutritional n-3 PUFA deficiency.SIGNIFICANCE STATEMENT In a mouse model mimicking n-3 PUFA dietary deficiency during adolescence and adulthood, we found strong increases in anxiety and anhedonia which lead to decreases in specific cognitive functions in adulthood. We found that endocannabinoid/mGlu5-mediated LTD and NMDAR-dependent LTP were lacking in adult n-3-deficient mice. Acute positive allosteric modulation of mGlu5 or inhibition of endocannabinoid degradation normalized behaviors and synaptic functions in n-3 PUFA-deficient adult mice. These findings have important implications for the identification of nutritional risk for disease and the design of new treatments for the behavioral deficits associated with nutritional n-3 PUFAs' imbalance.

In rearing, ducks can express unwanted behaviours such as nervousness and feather pecking. Numerous studiesrealised with humans and rodent models showed a positive effect of long chain polyunsaturated fatty acids n-3(LC PUFA n-3) on the brain development and functioning. The aim of this trial was to test the possibility ofdecreasing the pecking behaviour of Muscovy duck in rearing by providing LC PUFA n-3 during embryonicand/or post hatch development of ducklings. The enrichment of eggs and thus embryos in LC PUFA n-3 wasrealized by feeding female ducks with a diet containing docosahexaenoic (DHA) and linolenic acids (microalgaeand linseed oil). A control group of female ducks was fed with a diet containing linoleic acid (soya oil). Afterhatching, starting and growing diets were also either enriched with DHA and linolenic acid, or with linoleic acid.Several behaviour tests were realized between 1 and 3 weeks of age to analyze the adaptation capacity ofducklings. The growth performance, time budget, social interactions, feathering kinetic and pecking behaviour,were regularly recorded during the rearing period of ducklings. We found no significant interaction between thetwo factors. Ducklings issued from female ducks fed a diet enriched with n-3 FA had higher body weight at D0,D28 and D56, lower feed conversion ratio for the growing period and lower reactivity to stress than ducklingsissued from female ducks fed a diet enriched with n-6 FA. The enrichment with LC PUFA n-3 of diet distributedto female ducks reduced the frequency and the gravity of feather pecking of offspring. Moreover, diets enrichedwith LC PUFA n-3 and distributed during the starting and growing periods had positive effects on bonemineralization of ducklings and FA composition of thigh muscles measured at 84 days of age., En élevage, les canards peuvent exprimer des comportements délétères tels que le nervosisme et le picage. De nombreux travaux conduits chez l’homme et des modèles rongeurs ont montré un effet positif des acides gras polyinsaturés n-3 à longue chaîne (AGPI n-3 LC) sur le développement et le fonctionnement du cerveau.L’objectif de cet essai est de tester la possibilité de diminuer le comportement de picage du canard de Barbarie en élevage en apportant des AGPI n-3 LC au cours du développement soit embryonnaire soit post-natal des canetons, en croisant ces deux facteurs. L’enrichissement des oeufs et donc des embryons en AGPI n-3 LC est réalisé en alimentant les canes avec un régime contenant les acides docosahexaénoique (DHA) et linolénique (microalgues et huile de lin). Un lot témoin de canes est alimenté avec un régime contenant de l’acide linoléique (huile de soja). Après éclosion, les aliments démarrage et croissance sont aussi soit enrichis avec du DHA et de l’acide linolénique, soit avec de l’acide linoléique. Plusieurs tests de comportement sont réalisés entre 1 et 3 semaines pour analyser la capacité d’adaptation des canetons. Les performances de croissance, le budget temps, les interactions sociales, la cinétique d’emplumement et le comportement de picage sont enregistrés régulièrement au cours de la période d’élevage des canetons. Aucune interaction entre les deux facteurs n’est observée. Les canetons issus des canes alimentées avec un régime enrichi en AG n-3 ont un poids vif supérieur à J0, J28 et J56, un indice de consommation, pour la période de croissance, inférieur et une moindre réactivité au stress. Ils présentent également une fréquence et une gravité du picage moindres. De plus, l’aliment enrichi en AGPI n-3 LC, distribué pendant les périodes de démarrage et de croissance, a un effet positif sur la minéralisation osseuse des canards et sur le profil en acides gras des muscles de la cuisse mesurés à 84 jours.

Docosahexaenoic acid (DHA, 22:6n-3) is an essential omega-3 polyunsaturated fatty acid (PUFA). It is specifically enriched in the brain and the retina and it is required for visual acuity, proper brain development and cerebral functions. While DHA deficiency in the brain was shown to be linked to the emergence of cerebral diseases (i.e. Alzheimer’s disease or Parkinson’s disease), studies showed that a dietary intake of omega-3 PUFA could prevent or attenuate neurologic disturbances linked with ageing or neurodegenerative diseases. In this context, it is primary to deliver DHA efficiently to the brain. Targeting the brain with DHA might offer great promise in developing new therapeutics for neurodegenerative diseases. The French host laboratory previously synthesized a stabilized form of lysophosphatidylcholine-DHA, which is main vector of DHA transportation to the brain, of structure 1-acetyl,2-docoshexaenoyl-glycerophosphocholine, patented and named AceDoPC®. Injection of AceDoPC or DHA after experimental ischemic stroke showed that both molecules also had neuroprotective effects. These potential neuroprotective effects are expected to be due, in part, to DHA conversion into oxygenated metabolites. This study aims to investigate the beneficial effects of DHA and its derived metabolites either unesterified or esterified within structured phospholipids on a model of neurogenesis in vitro under physiological or pathological conditions. The first objective of this work was then to synthesize the DHA-containing structured phospholipid AceDoPC®, DHA oxygenated derivative protectin DX (PDX) and a novel structured phospholipid of protectin: 1-acetyl,2-protectinDX-glycerophosphocholine (AceDoxyPC). The second objective was to investigate the effects of DHA, AceDoPC and PDX on neurogenesis using an in vitro model of neurogenesis, namely cultures of neural stem progenitor cells (NSPCs) derived from the adult mouse brain under physiological or pathological conditions (ischemic conditions). Following this, the third objective of this work was to identify the mechanisms involved in such response to stress induced under pathological conditions. Synthesis of the novel structured phospholipid AceDoxyPC was successfully performed by double enzymatic lipoxygenation of AceDoPC and identification of the product was possible using advanced techniques of liquid chromatography (LC)/electrospray ionization (/ESI)/mass spectrometry (/MS). Future studies on this potential neuroprotective molecule transporter are to be investigated in the near future. Neurogenesis study of cell cultures with AceDoPC showed enhanced neurogenesis compared to addition of unesterified DHA or vehicle control, especially under pathological conditions. Preliminary studies of the potential mechanisms involved in neuroprotection hinted that AceDoPC neuroprotective and regenerative effects might be due in part to its anti-oxidative effects., L'acide docosahexaénoïque (DHA, 22:6n-3) est un acide gras polyinsaturé (AGPI) oméga-3. Il est particulièrement abondant dans le cerveau et la rétine et est nécessaire pour le bon développement et fonctionnement du cerveau. Tandis qu'une déficience en DHA a été montrée être liée à l'émergence de maladies cérébrales (i.e. maladie d'Alzheimer ou maladie de Parkinson), des études ont également montré qu'un apport alimentaire en AGPI oméga-3 pouvait empêcher ou atténuer les perturbations neurologiques liées au vieillissement ou aux maladies neurodégénératives. Il est alors primordial de transporter efficacement le DHA au cerveau. Le laboratoire français a synthétisé auparavant une forme stabilisée de la lysophosphatidylcholine-DHA, qui est le vecteur principal d'apport de DHA au cerveau, de structure 1-acétyl,2-docosahexaénoyl-glycérophosphocholine, brevetée et nommée AceDoPC®. L'injection d'AceDoPC ou de DHA après un accident vasculaire cérébral ischémique provoqué expérimentalement a montré que ces deux molécules étaient neuroprotectrices. Ces effets sont supposés être dus en partie à la conversion du DHA en métabolites oxygénés. Notre étude vise à examiner les effets du DHA et de ses métabolites dérivés, estérifiés ou non dans des phospholipides structurés sur un modèle de neurogenèse in vitro en conditions physiologiques ou pathologiques. Le premier objectif de ce travail a été de synthétiser le phospholipide structuré contenant du DHA, l’AceDoPC®, la protectine DX (métabolite oxygéné du DHA), et un nouveau phospholipide structuré contenant la protectine: 1-acétyl,2-protectine DX-glycérophosphocholine (AceDoxyPC). Le second objectif était d’étudier les effets du DHA, de l'AceDoPC et de la PDX sur la neurogenèse en utilisant un modèle in vitro de neurogenèse, constitué de cultures de cellules souches progénitrices neurales (NSPCs) dérivées de cerveaux de souris adultes, dans des conditions physiologiques ou pathologiques (ischémiques ici). Enfin, le troisième objectif de cette thèse a été d'identifier les mécanismes impliqués dans la réponse des cellules aux conditions ischémiques. La synthèse du phospholipide structuré AceDoxyPC a été réalisée avec succès par une double lipoxygénation enzymatique de l'AceDoPC, et l'identification du produit a été possible grâce à l'utilisation de techniques avancées de chromatographie liquide couplée à la spectrométrie de masse (LC/ESI/MS). De futures études sur ce transporteur de molécule neuroprotectrice potentielle doivent être réalisées prochainement. Les cellules incubées en présence d’AceDoPC présentent une augmentation de neurogenèse comparativement à celles cultivées avec addition de DHA non estérifié ou du véhicule contrôle, notamment sous conditions pathologiques. Les études préliminaires des mécanismes potentiellement impliqués dans la neuroprotection indiquent que les effets neuroprotecteurs et régénératifs de l'AceDoPC pourraient être en partie dus à des effets anti-oxidants.

PMCID: PMC5666899; International audience; Argan oil is widely used in Morocco in traditional medicine. Its ability to treat cardiovascular diseases is well-established. However, nothing is known about its effects on neurodegenerative diseases, which are often associated with increased oxidative stress leading to lipid peroxidation and the formation of 7-ketocholesterol (7KC) resulting from cholesterol auto-oxidation. As 7KC induces oxidative stress, inflammation and cell death, it is important to identify compounds able to impair its harmful effects. These compounds may be either natural or synthetic molecules or mixtures of molecules such as oils. In this context: (i) the lipid profiles of dietary argan oils from Berkane and Agadir (Morocco) in fatty acids, phytosterols, tocopherols and polyphenols were determined by different chromatographic techniques; and (ii) their anti-oxidant and cytoprotective effects in 158N murine oligodendrocytes cultured with 7KC (25-50 mu M; 24 h) without and with argan oil (0.1% v/v) or -tocopherol (400 mu M, positive control) were evaluated with complementary techniques of cellular and molecular biology. Among the unsaturated fatty acids present in argan oils, oleate (C18:1 n-9) and linoleate (C18:1 n-6) were the most abundant; the highest quantities of saturated fatty acids were palmitate (C16:0) and stearate (C18:0). Several phytosterols were found, mainly schottenol and spinasterol (specific to argan oil), cycloartenol, beta-amyrin and citrostadienol alpha- and gamma-tocopherols were also present. Tyrosol and protocatechic acid were the only polyphenols detected. Argan and extra virgin olive oils have many compounds in common, principally oleate and linoleate, and tocopherols. Kit Radicaux Libres (KRL) and ferric reducing antioxidant power (FRAP) tests showed that argan and extra virgin olive oils have anti-oxidant properties. Argan oils were able to attenuate the cytotoxic effects of 7KC on 158N cells: loss of cell adhesion, cell growth inhibition, increased plasma membrane permeability, mitochondrial, peroxisomal and lysosomal dysfunction, and the induction of oxiapoptophagy (OXIdation + APOPTOsis + autoPHAGY). Altogether, our data obtained in 158N oligodendrocytes provide evidence that argan oil is able to counteract the toxic effects of 7KC on nerve cells, thus suggesting that some of its compounds could prevent or mitigate neurodegenerative diseases to the extent that they are able to cross the blood-brain barrier.

Dans les pays industrialisés, les pathologies oculaires à composante vasculaires, que ce soit la rétinopathie du prématuré (ROP), la rétinopathie du diabétique ou la dégénérescence lié à l’âge, représentent la première cause de cécité respectivement chez l’enfant, l’adulte et la personne âgée. Plusieurs études sur l’homme ou sur des modèles animaux ont souligné le rôle crucial joué des acides gras polyinsaturés (AGPI) au cours de ces rétinopathies et notamment l’action préventive des acides gras polyinsaturés oméga 3 (AGPI n-3) sur l’angiogenèse pathologique. Ces AGPI sont estérifiés dans les glycérophospholipides constituant les membranes cellulaires. On les retrouve également dans une classe particulière de glycérophospholipides, les plasmalogènes. La particularité des plasmalogènes réside dans leur liaison vinyl-éther en position sn-1 au lieu d’une liaison ester dans les autres glycérophospholipides. Les AGPI sont libérés des plasmalogènes par une phospholipase indépendante au calcium, la iPLA2, pour devenir des métabolites actifs. Les plasmalogènes via la libération des AGPI joueraient un rôle dans la mise en place et la maturation du réseau vasculaire rétinien et ce, notamment grâce à la bonne mise en place du réseau astrocytaire. Les astrocytes et les cellules de Müller sont les cellules macrogliales qui servent de soutien physique et métabolique à la rétine. De plus, les cellules de Müller participent au métabolisme des lipides. L’objectif de ce travail de thèse a été d’évaluer l’implication des plasmalogènes dans le métabolisme des cellules de Müller et des astrocytes mais aussi dans la communication entre ces cellules macrogliales. Nous avons également étudié le profil lipidique d’enfants prématurés pour mettre en évidence de potentielles altérations du métabolisme des plasmalogènes chez des nouveau-nés développant une rétinopathie à composante vasculaire, la rétinopathie du prématuré (ROP). Pour ce faire nous avons étudié les effets d’une diminution en plasmalogènes et/ou en iPLA2 sur des cellules de Müller en culture primaire après avoir préalablement vérifié l’expression de l’enzyme clef de la biosynthèse des plasmalogènes. Nous avons ensuite étudié les effets d’une diminution des teneurs en plasmalogènes sur la communication calcique entre les cellules de Müller et les astrocytes. Nos résultats ont montré que les cellules de Müller expriment l’enzyme-clé de synthèse des plasmalogènes et que ces cellules sont plus riches en plasmalogènes que la rétine entière. Les plasmalogènes seraient impliqués dans le contrôle de la migration des cellules de Müller par l’action de la voie ERK1/2 MAPK. Ces effets ne semblent pas passer par la libération des AGPI. De plus nos résultats suggèrent une dégradation de la communication entre les astrocytes et les cellules de Müller en cas de diminution des teneurs en plasmalogènes dans les cellules de Müller. Enfin chez l’homme nous avons mis en évidence une accumulation des AGPI n-6 au détriment des AGPI n-3 dans les érythrocytes des enfants développant une rétinopathie du prématuré et inversement dans le groupe d’enfants prématuré contrôle. L’ensemble de ces travaux confirme l’importance du métabolisme lipidique, et plus particulièrement celui des plasmalogènes, sur le fonctionnement de la rétine., Retinal vascular disorders such as retinopathy of prematurity (ROP), diabetic retinopathy or age-related macular degeneration represent the first cause of vision loss at all ages in industrialized countries. Many epidemiological or animal studies have shown the involvement of polyunsaturated fatty acids (PUFA) in the regulation of vascular development and more specifically the beneficial properties of omega 3 PUFA (n-3 PUFA) against pathological vascularization. Those PUFA are esterified on glycerophospholipids (GP). GP are the primary constituents of the lipid bilayer of cell membranes. PUFA can be also esterified on a specific class of GP, called plasmalogens. Plasmalogens are characterized by the presence of a vinyl ether linkage at the sn-1 position of glycerol instead of an ester linkage as seen in other GP. PUFA are released from plasmalogens by a calcium-independent phospholipase (iPLA2). Free PUFA can be converted into biologically active metabolites. Plasmalogens may have an impact on the development and the maturation of retinal vascular network through the PUFA they release through the control of astrocyte template formation prior to vessel formation. Astrocytes and Müller cells are macroglials cells providing physical and metabolic supports to the retina. Müller cells are key actors of the retinal lipid metabolism. The aim of this work was to evaluate the involvement of plasmalogens in Müller cells and astrocytes metabolism as well as in the ability of these cells to communicate. On one hand, we have studied the effects of a decrease in plasmalogen biosynthesis and/or in iPLA2 activity on Müller cell physiology. Müller cells express a biosynthesis key enzyme of plasmalogen and reducing the biosynthesis of plasmalogens affects Müller cell ability to migrate through the ERK1/2 MAPK signalling. In a second series of studies, we studied the repercussions of such modifications on Müller cell physiology on their ability to communicate with retinal astrocytes through calcium signalling. Our results suggest that affecting plasmalogen metabolism in Müller cells alters the communication between astrocytes and Müller cells. Finally, and in order to investigate whether plasmalogen metabolism may be modified in a human disease displaying abnormal retinal vascular development, we performed a lipidomic study of circulating lipids in infants affected by retinopathy of prematurity. ROP was characterized by the accumulation of n-6 PUFA at the expense of n-3 PUFA, these changes being associated to plasmalogens. All these experiments confirm the importance of lipid metabolism, and especially plasmalogens, on the retina functioning.

Secoisolariciresinol (SECO) is a natural antioxidant lignan accumulated in large amounts in the seedcoat of flax and retained in the flaxseed cake residue during linseed oil pressing. Here SECO was extracted and purified from flaxseed cake and assayed for its ability to prevent oxidation of linseed oil and an o/w emulsion containing linseed oil. For this purpose, an accelerated storage (Schaal oven) test was performed and SECO effectiveness was compared to that of two antioxidants commonly used in food and cosmetic products: α-tocopherol (α-TOCO) and butylated hydroxyanisole (BHA). In our hands, SECO addition, ranging from 50 to 500 μmole per kg oil, significantly decreased the production of both primary (conjugated dienes, CD) and secondary (thiobarbituric acid-reactive substances, TBARS) oxidation products. This study evidenced that SECO is an effective stabilizer of linseed oil and its o/w emulsion and this protective effect outperformed both the natural α-TOCO and the synthetic BHA antioxidants. In particular, SECO was the most effective in the protection of the o/w emulsion against secondary oxidation products, which makes it a potential alternative preservative for oily products in foods and cosmetics. Practical applications: The present study could lead to applications in the food and cosmetic industries for the stabilization of o/w emulsions. Addition of SECO to linseed oil, already rich in ω-3, could also result in a new functional food with synergistic beneficial actions on human health.

A meta-analysis on the influence of dietary lipid or fatty acid (FA) contents on beef FA composition was conductedusing the “ω3Meat” database. This database contains bibliographic data posterior to year 2000 related to the impact ofcattle farming system parameters on beef FA composition. The results of the meta-analysis pointed that 1) Theproportion of C18:3 n-3 present in cattle muscle is directly proportional to its percentage in the diet and to the fatcontent of the diet, 2) Diet lipid content seems to be the most important factor of variation of n-6 PUFA and trans FApresent in cattle muscle. Thus, meta-analysis is a useful tool to assess and summarize the knowledge to accuratelypredict FA composition of ruminant meat even in rearing conditions.

The aim of this study was to develop prediction equations for determining n-6 and n-3 polyunsaturated fatty acid(PUFA) content in beef to serve the industry as a complementary tool alongside near-infrared spectrometry (NIRS) forassessing the nutritional quality of beef carcasses as a starting point for a beef carcass classification scheme. This studyhad two objectives: 1) to predict the n-6 and n-3 PUFA composition of beef using saturated fatty acids (SFA),monounsaturated fatty acids (MUFA) and total PUFA contents together with livestock-related data from slaughterhouserecords and 2) to validate these equations by data predicted by NIRS. Very satisfactory prediction equations wereobtained (R²>0.9) and validated (R²>0.75) for total n-6 PUFA and 18:2 n-6. For total n-3 PUFA and 18:3 n-3,prediction equations yielded R² value of 0.77 but they were not validated with data predicted by NIRS.

Présentation «flash» : projet de recherche (Oxylino) en cours inter-collaboratif du Dr Frédéric Capel; National audience

Aim/hypothesis: Insulin resistance (IR) favors the progression of metabolicsyndrome (MetS) and increases the risk of type2 diabetes. IR results from metabolic dysfunctions,oxidative stress and inflammation caused by ectopic fat depots. We studied the effect of canola oil enriched with micronutrients naturally present in canola seed on IR and MetS during a high fat (HF)-challenge]. [br/] Research design and Methods: Rats were fed with a HF diet containing 30% of lipids, mainly derived from palm oil (diet P) or from a mixture of palm and canola oils (60:40, diet C). In 2 groups of animals, diet C was further supplemented with alpha tocopherol, CoQ with or without Canolol (diets CMC & CM respectively). Insulin sensitivity and glucose tolerance were assessed after 10 weeks. Tissue sampling was carried at sacrifice for gene expression analysis (RT-qPCR), protein expression level (Western-Blot), fatty acid composition (Gas Chromatography). HF animals were compared to control animals receiving a standard diet. ANOVA was performed for statistical analysis (followed by adjusted Fisher post-hoc test when p

Le fichier contient le book of abstracts; Insulin resistance (IR) favors the progression of metabolic syndrome (MetS) and increases the risk of type 2 diabetes. IR results from metabolic dysfunctions, oxidative stress and inflammation caused by ectopic fat depots. We studied the effect of canola oil enriched with micronutrients naturally present in canola seed on IR and MetS during a high fat (HF)-challenge. Rats were fed with a HF diet containing 30% of lipids, mainly derived from palm oil (diet P), or from a mixture of palm and canola oils (60:40, diet C). In 2 groups of animals, diet C was further supplemented with alpha tocopherol, CoQ with or without Canolol, (diets CMC & CM respectively). Insulin sensitivity and glucose tolerance were assessed after 10 weeks. HF animals were compared to control animals receiving a standard diet. All groups receiving a HF diet gained significantly more weight compared to control. Similar results were obtained for fat depots. Glucose tolerance was altered in P and C groups and improved in CM and CMC. Insulin sensitivity was not different between control and P groups, but was higher in CMC group compared to controls. A reduced activation of PDK4 and Srebp1c expression was observed in skeletal muscle in CM group. In conclusion, the proportion of AGPI could not prevent metabolic disturbance induced by a HF meal. Enrichment with natural micronutrients could prevent insulin resistance and glucose intolerance which could be mediated by a better glucose oxidation in skeletal muscle

The aim of the study was to determine the effect of maternal diets administered since day 1 of gestation and containing dairy lipids or vegetable oils differing in the supply of n-3 polyunsaturated fatty acids (n-3 PUFAs) (equilibrated or deficient) and of Lactobacillus fermentum (L. fermentum) on the docosahexaenoic acid (DHA) accretion in the pups at postnatal day 14 in the prefrontal cortex (PFC) and hippocampus (HC) for brain structures and in the liver and adipose tissue for peripheral tissues. Maternal milk fatty acid composition was also assessed by analyzing the fatty acid composition of the gastric content of the pups. DHA was higher in mice supplemented with L. fermentum than in mice in the deficient group in HC and PFC and also in liver and adipose tissue. This increase could be linked to the slight but significant increase in C18:3n-3 in the maternal milk. This proportion was comparable in the dairy lipid group for which the brain DHA level was the highest. L. fermentum may have a key role in the protection of the brain during the perinatal period via the neuronal accretion of n-3 PUFAs, especially during n-3 PUFA deficiency.

Insulin resistance (IR) favors the progression of metabolic syndrome (MetS) and increases the risk of type 2 diabetes. IR results from metabolic dysfunctions, oxidative stress and inflammation caused by ectopic fat depots. We studied the effect of canola oil enriched with micronutrients naturally present in canola seed on IR and MetS during a high fat (HF)-challenge. Rats were fed with a HF diet containing 30% of lipids, mainly derived from palm oil (diet P), or from a mixture of palm and canola oils (60:40, diet C). In 2 groups of animals, diet C was further supplemented with alpha tocopherol, CoQ with or without Canolol, (diets CMC & CM respectively). Insulin sensitivity and glucose tolerance were assessed after 10 weeks. HF animals were compared to control animals receiving a standard diet. All groups receiving a HF diet gained significantly more weight compared to control. Similar results were obtained for fat depots. Glucose tolerance was altered in P and C groups and improved in CM and CMC. Insulin sensitivity was not different between control and P groups, but was higher in CMC group compared to controls. A reduced activation of PDK4 and Srebp1c expression was observed in skeletal muscle in CM group. In conclusion, the proportion of AGPI could not prevent metabolic disturbance induced by a HF meal. Enrichment with natural micronutrients could prevent insulin resistance and glucose intolerance which could be mediated by a better glucose oxidation in skeletal muscle

The liver plays a central role in the regulation of fatty acid metabolism, which is highly sensitive to transcriptional responses to nutrients and hormones. Transcription factors involved in this process include nuclear hormone receptors. One such receptor, PPARα, which is highly expressed in the liver and activated by a variety of fatty acids, is a critical regulator of hepatic fatty acid catabolism during fasting. The present study compared the influence of dietary fatty acids and fasting on hepatic PPARα-dependent responses. Pparα(-/-) male mice and their wild-type controls were fed diets containing different fatty acids for 10 weeks prior to being subjected to fasting or normal feeding. In line with the role of PPARα in sensing dietary fatty acids, changes in chronic dietary fat consumption influenced liver damage during fasting. The changes were particularly marked in mice fed diets lacking essential fatty acids. However, fasting, rather than specific dietary fatty acids, induced acute PPARα activity in the liver. Taken together, the data imply that the potent signalling involved in triggering PPARα activity during fasting does not rely on essential fatty acid-derived ligand. Published version

International audience; Several genetic causes of autism spectrum disorder (ASD) have been identified. However, more recent work has highlighted that certain environmental exposures early in life may also account for some cases of autism. Environmental insults during pregnancy, such as infection or malnutrition, seem to dramatically impact brain development. Maternal viral or bacterial infections have been characterized as disruptors of brain shaping, even if their underlying mechanisms are not yet fully understood. Poor nutritional diversity, as well as nutrient deficiency, is strongly associated with neurodevelopmental disorders in children. For instance, imbalanced levels of essential fatty acids, and especially polyunsaturated fatty acids (PUFAs), are observed in patients with ASD and other neurodevelopmental disorders (e.g., attention deficit hyperactivity disorder (ADHD) and schizophrenia). Interestingly, PUFAs, and specifically n-3 PUFAs, are powerful immunomodulators that exert anti-inflammatory properties. These prenatal dietary and immunologic factors not only impact the fetal brain, but also affect the microbiota. Recent work suggests that the microbiota could be the missing link between environmental insults in prenatal life and future neurodevelopmental disorders. As both nutrition and inflammation can massively affect the microbiota, we discuss here how understanding the crosstalk between these three actors could provide a promising framework to better elucidate ASD etiology.

With the ageing population and increased cases of neurodegenerative diseases, there is a crucial need for the development of new nutritional approaches to prevent and delay the onset of cognitive decline. Neuroinflammatory processes contribute to neuronal damage that underpins neurodegenerative disorders. Growing evidence sheds light on the use of dietary n-3 long chain polyunsaturated fatty acids to improve cognitive performances and reduce the neuroinflammatory responses occurring with age and neurodegenerative pathologies. This review will summarise the most recent information related to the impact and mechanisms underlying the neuroinflammatory processes in cognitive disorders. We will also discuss the mechanisms underlying n-3 polyunsaturated fatty acids effect on neuroinflammation and memory decline., Le développement d’approches nutritionnelles pertinentes pour prévenir et retarder l’apparition du déclin cognitif est un enjeu important, compte tenu du vieillissement de la population et de l’augmentation de l’incidence des maladies neurodégénératives. Les processus neuro-inflammatoires contribuent aux mécanismes neuropathologiques impliqués dans les troubles neurodégénératifs et de la cognition. Des données récentes indiquent l’importance des acides gras polyinsaturés n-3 alimentaires dans le maintien des performances mnésiques et la régulation de la neuroinflammation liée à l’âge ou à la maladie d’Alzheimer. Dans cette revue, seront présentées des données récentes sur les liens existants entre le statut nutritionnel en acides gras polyinsaturés n-3, les processus neuro-inflammatoires et les troubles cognitifs associés, ainsi que les mécanismes qui pourraient être impliqués dans les effets protecteurs de ces acides gras.

Among omega-3 polyunsaturated fatty acids (PUFAs), docosahexaenoic acid (DHA, 22:6n-3) is important for adequate brain development and cognition. DHA is highly concentrated in the brain and plays an essential role in brain functioning. DHA, one of the major constituents in fish fats, readily crosses the blood brain barrier from blood to the brain. Its critical role was further supported by its reduced levels in the brain of Alzheimer's disease (AD) patients. This agrees with a potential role of DHA in memory, learning and cognitive processes. Since there is yet no cure for dementia such as AD, there is growing interest in the role of DHA-supplemented diet in the prevention of AD pathogenesis. Accordingly, animal, epidemiological, preclinical and clinical studies indicated that DHA has neuroprotective effects in a number of neurodegenerative conditions including AD. The beneficial effects of this key omega-3 fatty acid supplementation may depend on the stage of disease progression, other dietary mediators and the apolipoprotein ApoE genotype. Herein, our review investigates, from animal and cell culture studies, the molecular mechanisms involved in the neuroprotective potential of DHA with emphasis on AD.

The 3C Study supports are listed on the Study website (www.three-city-study.com). The fatty acid analyses performed by EP were supported by the Conseil Regional d'Aquitaine. EF was supported by the Fondation Recherche Medicale through grant number DEA20120624709; Background & aims: Nutritional factors, such as fatty acids (FA), could modulate physical performance in the elderly. In particular, the opposite properties of long-chain n-3 and n-6 polyunsaturated FAs (LC PUFAs) could impact muscle function. We aimed to assess the cross-sectional association between plasma FAs and gait speed in French elderly community-dwellers.Methods:Elderly participants from the Bordeaux centre of the Three-City Study were included. The proportion of 12 FAs, and gait speed (m/s) were measured concomitantly at enrollment. Low gait speed (LGS) was defined as below the first quartile of gait speed. FA patterns were derived from the 12 individual FAs using principal component analysis. Multivariate logistic regression models were used and odds-ratios (OR) were expressed per one additional standard-deviation unit of each plasma FA or per one additional unit of pattern score.Results: Among 982 participants, 239 (243%) had a low gait speed (

International audience; Two experiments were conducted using crossbred Salers x Charolais fattening steers fed diets enriched with no supplemental oilseeds or oils rich in either n-6 PUFA (from sunflower seeds) or n-3 PUFA (from linseeds) provided either as seeds incorporated in the diet (i.e., not protected from ruminal bacterial hydrogenation) or by chronic infusion into the duodenum (protected form). In the Sunflower experiment, animals (initial age = 454 +/- 20 d; initial BW = 528 +/- 36 kg) received a control diet for 70 d (CS, n = six) consisting of hay and concentrate, or the same basal diet supplemented with sunflower oil (4% of dietary DM), either fed as seeds (SS, n = six) or infused into the duodenum (ISO, n = six). The same experimental design was applied to animals (initial age = 412 +/- 33 d; initial BW = 536 +/- 33 kg) used in the Linseed experiment (CL, LS, and ILO; n = 8 per group). For all animals, blood was sampled every 15 d during 70 d. In both trials, a significant diet x time interaction (P < 0.001) was detected for plasma concentrations of apolipoprotein A-I, phospholipids, and free and esterified cholesterol, with values increasing with time during administration of the PUFA-rich diets being more evident with ISO and ILO diets. Plasma fatty acids were altered with oil infusions, with increased concentrations of n-6 (1.6-fold; P < 0.05) and n-3 PUFA (4.5-fold; P < 0.05) and of their respective indicies of peroxidizability (1.2- and 1.5-fold with Diets ISO and ILO, respectively; P < 0.05). In vitro copper-induced peroxidation of lipids revealed a decreased length of the lag phase in the process of conjugated diene generation by 48% (P < 0.005) with the ILO diet, indicating less resistance against peroxidation than in control steers. Compared with CS, the ISO treatment increased plasma alpha-tocopherol (x2.5; P < 0.05) leading to similar resistance against peroxidation. After depletion of this vitamin, the rates of peroxidation and production of conjugated dienes were greater (twofold; P < 0.05) with the ISO and ILO diets than with the others. In conclusion, infusion of sunflower or linseed oil into the duodenum altered the composition and distribution of plasma lipids and increased the plasma concentration of PUFA. The sensitivity of plasma PUFA to peroxidation depends on the plasma level of antioxidants, especially vitamin E, a nutrient important both for the health of animals and for the stability of the blood lipids until their tissue deposit.

Les acides gras polyinsaturés (AGPI) de type n-6 et n-3 sont connus pour leurs propriétés bénéfiques pour l'Homme. Mais ces composés sont également très sensibles à la peroxydation. Les produits terminaux de la lipoperoxydation sont le 4-hydroxy-2-nonénal (HNE) et le 4-hydroxy-2-hexénal (HHE) respectivement. Ces composés sont très réactifs ce qui leur permet de moduler l’expression génique en se fixant sur des protéines ou directement sur l’ADN. Par contre, ils peuvent aussi s’avérer cytotoxiques lorsqu’ils sont produits en excès. Ils existent sous deux formes, une forme libre et une forme liée notamment à des protéines. Nous avons mis au point une méthode d’extraction conjointe du HNE et du HHE sous leurs deux formes pour leur quantification par CPG-SM/SM. Nous avons également proposé différentes adaptations de la méthode en fonction des matrices testées. Enfin, certaines performances des méthodes proposées ont été évaluées par l'approche du profil d’exactitude.

In higher plants, fatty acids (FAs) with 18 carbons (18C) represent about 70% of total FAs, the most abundant species being 18:2 and 18:3. These two polyunsaturated FAs (PUFAs) represent about 55% of total FAs in Arabidopsis cell suspension cultures, whereas 18:1 represents about 10%. The level of PUFAs may vary, depending on ill-defined factors. Here, we compared various sets of plant cell cultures and noticed a correlation between the growth rate of a cell population and the level of unsaturation of 18C FAs. These observations suggest that the final level of PUFAs might depend in part on the rate of cell division and that FAD2 and FAD3 desaturases, which are respectively responsible for the formation of 18:2 and 18:3 on phospholipids, have limiting activities in fast-growing cultures. In plant cell culture, phosphate (Pi) deprivation is known to impair cell division and to trigger lipid remodeling. We observed that Pi starvation had no effect on the expression of FAD genes and that the level of PUFAs in this situation was also correlated with the growth rate. Thus, the level of PUFAs appears as a hallmark in determining cell maturity and aging.

Long-term intake of dietary fatty acids is known to predispose to chronic inflammation, but their effects on acute intestinal ischaemia/reperfusion (I/R) injury is unknown. The aim of this study was to determine the consequences of a diet rich in n-3 or n-6 polyunsaturated fatty acids (PUFA) on intestinal I/R-induced damage. Mice were fed three different isocaloric diets: a balanced diet used as a control and two different PUFA-enriched diets, providing either high levels of n-3 or of n-6 PUFA. Intestinal injury was evaluated after intestinal I/R. PUFA metabolites were quantitated in intestinal tissues by LC-MS/MS. In control diet-fed mice, intestinal I/R caused inflammation and increased COX and lipoxygenase-derived metabolites compared with sham-operated animals. Lipoxin A4 (LxA4 ) was significantly and selectively increased after ischaemia. Animals fed a high n-3 diet did not display a different inflammatory profile following intestinal I/R compared with control diet-fed animals. In contrast, intestinal inflammation was decreased in the I/R group fed with high n-6 diet and level of LxA4 was increased post-ischaemia compared with control diet-fed mice. Blockade of the LxA4 receptor (Fpr2), prevented the anti-inflammatory effects associated with the n-6 rich diet. This study indicates that high levels of dietary n-6, but not n-3, PUFAs provides significant protection against intestinal I/R-induced damage and demonstrates that the endogenous production of LxA4 can be influenced by diet.

In this study, we designed a specific, continuous, and sensitive UV spectrophotometric lipase assay using natural triacylglycerols (TAGs) from the Aleurites fordii seed oil (tung oil). alpha-Eleostearic acid (9,11,13-cis, trans,trans-octadecatrienoic acid) is the main fatty acid component (it accounts for up to 70%) of the TAGs from tung oil. The conjugated triene present in alpha-eleostearic acid constitutes an intrinsic chromophore, which confers strong UV absorption properties on both the free fatty acid and the TAGs from tung oil. The lipase assay is based on the difference between the apparent molar extinction coefficients of the two types of alpha-eleostearic acid present, that which is esterified into TAGs and that which is released into the reaction medium. This difference is responsible for the variations in the UV absorption spectrum of the reaction medium occurring upon enzymatic TAGs hydrolysis. Using the purified lipase from Thermomyces lanuginosa (TLL) and the detergent sodium taurodeoxycholate (NaTDC, 4 mM), it was established that the most suitable method of measuring lipolysis consisted of monitoring the decrease in the OD at 292 nm, which was linear with time and proportional to the amount of lipase added. In order to be able to estimate the specific activity of TLL, we determined an apparent molar extinction coefficient of alpha-eleostearic acid (epsilon = 13,900 M(-1) cm(-1)) under the assay conditions. Amounts of pure TLL as small as 1 ng can be easily detected in the presence of 4 mM NaTDC. Interestingly, the NaTDC concentration can be decreased as far as 0.05 mM. In comparison with other well-known methods of lipase assay, the detection limit of this new method is 100-fold lower than with the pH-stat method and similar to that of a fluorescent assay recently developed at our laboratory.

International audience; Understanding how malnutrition contributes to depression is building momentum. In the present study we unravel molecular and cellular mechanisms by which nutritional disturbances lead to impaired emotional behaviour in mice. Here we report that nutritional n-3 polyunsaturated fatty acids (PUFA) deficiency induces a chronic stress state reflected by disrupted glucocorticoid receptor (GR)-mediated signalling pathway along with hypothalamic-pituitary-adrenal (HPA) axis hyperactivity. This hyperactivity in turn resulted in neuronal atrophy in the dorsolateral (dl)- and dorsomedial (dm)- prefrontal cortex (PFC) and subsequent mood-related behaviour alterations, similarly to chronic social defeat stress. Supplementation of n-3 PUFA prevented detrimental chronic social defeat stress-induced emotional and neuronal impairments by impeding HPA axis hyperactivity. These results indicate a role for dietary n-3 PUFA in the prevention of HPA axis dysfunction associated with the development of some neuropsychiatric disorders including depression.

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International audience

Foods rich in n-3 long chain polyunsaturated fatty acids (n-3 LC PUFA), like EPA and DHA have many nutritional benefits. EFSA recommendations are to consume 500 mg/day of EPA and DHA. But for a large population, actual intakes are lower than these recommendations. Different sources of n-3 LC PUFA for human consumption will be presented taking into accounts their sustainability or safety aspects. Different strategies to increase their bioavailability will be presented base on the molecular and supramolecular structures. Finally, the oxidative stability of n-3 fatty acids in foods will be raised from their manufacture to their digestion, and the metabolic consequences of the consumption of some of these oxidation products will be evoked., Les aliments riches en acides gras polyinsaturés n-3 à longues chaînes, comme l’EPA et le DHA présentent de nombreux bénéfices nutritionnels. Les recommandations de L’EFSA sont de consommer 500 mg/jour d’EPA et de DHA. Or pour une large population, les apports réels sont inférieurs à ces recommandations. Les différentes sources de n-3 pour l’alimentation humaine seront présentées en évoquant sur les aspects liés à la durabilité et à la sécurité. Seront ensuite présentées différentes pistes permettant d’augmenter leur biodisponibilité, en jouant sur les structures moléculaires et supramoléculaires. Enfin, la stabilité oxydative des acides gras n-3 dans les aliments sera évoquée depuis leur fabrication jusqu’à leur digestion, ainsi des résultats sur les conséquences métaboliques de la consommation des certains de ces produits d’oxydation.

The objective of this study was to determine fatty acid and cholesterol composition of Infraspinatus, Triceps brachii, Longissimus thoraces, Biceps femoris, Semitendinosus and Semimembranosus muscles from nine Bactrian carcasses (2-3 years of age). Bactrian camel muscles had significant differences in fatty acid and cholesterol contents between the six muscles. The total saturated fatty acids ranged between 29.4 mg/100g (SM) to 36.7 mgj100g (BF). Mono-unsaturated fatty acid ranged from 23.6 mgj100g (SM) to 26.3 mgj100g (IS) and poly-unsaturated fatty acids were between 14.2 mg/100g (IS) to 15.3 mg/100g (ST) significantly affected by muscle type. The cholesterol content of selected muscles varied between muscles. The highest value of cholesterol content found in Infraspinatus mucle (60 mgj100g), the lowest value for Semimembranosus muscle (43 mgj100g). Results showed muscle types significantly affect the fatty acid and cholesterol composition of Bactrian camel meat.

International audience; Epidemiological data suggest that a poor ω3 status favoured by the low ω3/ω6 polyunsaturated fatty acids ratio in western diets contributes to cognitive decline in the elderly, but mechanistic evidence is lacking. We therefore explored the impact of ω3 deficiency on the evolution of glutamatergic transmission in the CA1 of the hippocampus during aging by comparing 4 groups of rats aged 6-22 months fed ω3-deficient or ω3/ω6-balanced diets from conception to sacrifice: Young ω3 Balanced (YB) or Deficient (YD), Old ω3 Balanced (OB) or Deficient (OD) rats. ω3 Deficiency induced a 65% decrease in the amount of docosahexaenoic acid (DHA, the main ω3 in cell membranes) in brain phospholipids, but had no impact on glutamatergic transmission and astroglial function in young rats. Aging induced a 10% decrease in brain DHA, a 35% reduction of synaptic efficacy (fEPSP/PFV) due to decreased presynaptic glutamate release and a 30% decrease in the astroglial glutamate uptake associated with a marked astrogliosis (+100% GFAP). The ω3 deficiency further decreased these hallmarks of aging (OD vs. OB rats: -35% fEPSP/PFV P < 0.05, -15% astroglial glutamate uptake P < 0.001, +30% GFAP P < 0.01). This cannot be attributed to aggravation of the brain DHA deficit because the brains of OD rats had more DHA than those of YD rats. Thus, ω3 deficiency worsens the age-induced degradation of glutamatergic transmission and its associated astroglial regulation in the hippocampus.

n-3 polyunsaturated fatty acids (n-3 PUFA) contribute to the normal growth and development of numerous organs in the piglet. The fatty acid composition of piglet tissues is linked to the fatty acid composition of sow milk and, consequently, to the composition of sow diet during the gestation and lactation period. In this study, we investigated the impact of different contents of extruded linseed in the sow diet on the fatty acid composition and desaturase gene expression of piglets. Sows received a diet containing either sunflower oil (low 18:3n-3 with 18:3n-3 representing 3% of total fatty acids) or a mixture of extruded linseed and sunflower oil (medium 18:3n-3 with 9% of 18:3n-3) or extruded linseed (high 18:3n-3 with 27% of 18:3n-3) during gestation and lactation. Fatty acid composition was evaluated on sow milk and on different piglet tissues at days 0, 7, 14, 21 and 28. The postnatal evolution of delta5 (D5D) and delta6 (D6D) desaturase mRNA expression was also measured in the liver of low 18:3n-3 and high 18:3n-3 piglets. The milk of high 18:3n-3 sows had higher proportions of n-3PUFA than that of low 18:3n-3 and medium 18:3n-3 sows. Piglets suckling the high 18:3n-3 sows had greater proportions of 18:3n-3, 20:5n-3, 22:5n-3 and 22:6n-3 in the liver, and of 22:5n-3 and 22:6n-3 in the brain than low 18:3n-3 and medium 18:3n-3 piglets. D5D and D6D mRNA expressions in piglet liver were not affected by the maternal diet at any age. In conclusion, extruded linseed in the sow diet modifies the n-3PUFA status of piglets during the postnatal period. However, a minimal content of 18:3n-3 in the sow diet is necessary to increase the n-3PUFA level in piglet liver and brain. Moreover, modifications in the n-3PUFA fatty acid composition of piglet tissue seem linked to the availability of 18:3n-3 in maternal milk and not to desaturase enzyme expression.

Bacteria possess transcription regulators (of the TetR family) specifically dedicated to repressing genes for cytochrome P450, involved in oxidation of polyunsaturated fatty acids. Interaction of these repressors with operator sequences is disrupted in the presence of fatty acids, and they are therefore known as fatty-acid-displaced regulators. Here, we describe a novel mechanism of inactivating the interaction of these proteins with DNA, illustrated by the example of Bacillus subtilis regulator FatR. FatR was found to interact in a two-hybrid assay with TkmA, an activator of the protein-tyrosine kinase PtkA. We show that FatR is phosphorylated specifically at the residue tyrosine 45 in its helix-turn-helix domain by the kinase PtkA. Structural modelling reveals that the hydroxyl group of tyrosine 45 interacts with DNA, and we show that this phosphorylation reduces FatR DNA binding capacity. Point mutants mimicking phosphorylation of FatR in vivo lead to a strong derepression of the fatR operon, indicating that this regulatory mechanism works independently of derepression by polyunsaturated fatty acids. Tyrosine 45 is a highly conserved residue, and PtkA from B. subtilis can phosphorylate FatR homologues from other bacteria. This indicates that phosphorylation of tyrosine 45 may be a general mechanism of switching off bacterial fatty-acid-displaced regulators.

Objectives and Study: N-3 polyunsaturated fatty acids (PUFA) have many beneficial health effects, especially in neonates. We recently demonstrated that supplementation of the maternal diet with alpha-linolenic acid (C18:3 n-3) increases intestinal permeability at the end of the suckling period in piglets1. Education of the gut immune system towards the colonizing microbiota, and particularly towards lipopolysaccharides (LPS) is intense during this period. We hypothesized that the increased intestinal permeability observed with maternal n-3 PUFA would lead to increased transepithelial passage of LPS and modification of the gut immune system education towards this bacterial component. Methods: Two groups of sows were fed either a flaxseed-based (n-3 group) or a sunflower oil-based diet (n-6 group) during gestation and lactation. Piglets suckled their dam until post-natal day (PND) 28 when they were weaned on a regular weaning diet. From PND 14 to 28, a sub-group of piglets in each litter received an anti-gram negative bacteria antibiotic per os daily. At PND28 and 52, FITC-labeled LPS passage across the jejunum was evaluated ex vivo in Ussing chambers. Cultures of jejunal explants were used to evaluate cytokine secretion in response to LPS. Mononuclear cells were also isolated from mesenteric lymph nodes (MLN) and cultivated with LPS or concanavalin A. Results: At PND28, passage of FITC-LPS across the jejunum was increased in n-3 piglets (P

Session : Qualité des produits; absent

International audience; Omega-3 fatty acids are important for several neuronal and cognitive functions. Altered omega-3 fatty acid status has been implicated in reduced resistance to stress and mood disorders. We therefore evaluated the effects of repeated restraint stress (6 h/day for 21 days) on adult rats fed omega-3 deficient, control or omega-3 enriched diets from conception. We measured body weight, plasma corticosterone and hippocampus glucocorticoid receptors and correlated these data with emotional and depression-like behaviour assessed by their open-field (OF) activity, anxiety in the elevated-plus maze (EPM), the sucrose preference test and the startle response. We also determined their plasma and brain membrane lipid profiles by gas chromatography. Repeated restraint stress caused rats fed a control diet to lose weight. Their plasma corticosterone increased and they showed moderate behavioural changes, with increases only in grooming (OF test) and entries into the open arms (EPM). Rats fed the omega-3 enriched diet had a lower stress-induced weight loss and plasma corticosterone peak, and reduced grooming. Rats chronically lacking omega-3 fatty acid exhibited an increased startle response, a stress-induced decrease in locomotor activity and exaggerated grooming. The brain omega-3 fatty acids increased as the dietary omega-3 fatty acids increased; diets containing preformed long-chain omega-3 fatty acid were better than diets containing the precursor alpha-linolenic acid. However, the restraint stress reduced the amounts of omega-3 incorporated. These data showed that the response to chronic restraint stress was modulated by the omega-3 fatty acid supply, a dietary deficiency was deleterious while enrichment protecting against stress.

International audience

Modifying the lipid composition of milk and dairy products, to improve their nutritional properties, without negatively altering their technological, sensorial and functional qualities, constitutes a challenge for the dairy sector. This study was performed to increase the polyunsaturated fatty acids (PUFA) and decrease the saturated fatty acids (SFA) content of goats’ milk, under real field conditions and production, by means of altering the animals diet. The effect of these changes were characterised during the manufacture of soft ripened cheese and assessing the impact on physicochemical and sensorial characteristics. Two groups of 30 crossbreed Alpine dairy goats were fed either a control diet or a diet supplemented with oilseeds providing 50.4 g UFA.goat−1.day−1 or 69.6 g UFA.goat−1.day−1 which supplied respectively 1.4 and 2.4 % of alpha-linolenic acid (ALA). Supplementing the feed of dairy goats with PUFA was shown to have beneficial effects on the FA composition of goat’s milks and cheeses: (1) an increase in the content of ALA (18:3n-3; from 0.78 to 1.78 g.100 g−1 of total FA) and rumenic acid (main CLA; from 0.75 to 1.27 g.100 g−1 of total FA); (2) a decrease in the n-6/n-3 PUFA ratio (from 4.6 to 2) and the overall SFA content (from 66 to 60.4 g.100 g−1 of total FA). The corrected cheese yield was higher for the supplemented milks (16.3 %) in comparison to the control milks (15.4 %). Both cheeses showed a similar evolution in the levels of proteolysis and lipolysis with no flavour defects being detected. Cheese sensory scores for the two types of cheeses were similar. Hence, healthier goats’ milk and cheese FA profiles were obtained with good sensorial characteristics.

Un faible apport alimentaire en acides gras polyinsaturés (AGPI) de la série n-3 a été associé à la prévalence des troubles de l'humeur chez l’Homme. Chez les rongeurs, les approches nutritionnelles visant à modéliser une alimentation pauvre en AGPI n-3 ont largement été développées au siècle dernier. En effet, un régime alimentaire carencé en AGPI n-3 sur une ou plusieurs générations induit chez le rongeur des altérations des comportements émotionnels tels que des comportements de type dépressif ou anxieux. Nous avons montré au laboratoire Nutrineuro que des souris nourries avec un régime déficient en AGPI n-3 présentent des niveaux d’AGPI n-3, en particulier l'acide docosahexaénoïque (DHA, un AGPI n-3) plus faible dans le cortex préfrontal (PFC) et dans le noyau accumbens (NAc) par rapport aux souris contrôle. De plus, nous avons pu mettre en évidence qu’une alimentation déficiente en AGPI n-3 est capable de moduler la plasticité synaptique dépendante du système endocannabinoïde (eCB). De fait, la réduction de DHA dans le CPF et le NAc est accompagnée d'une altération de la dépression à long terme (LTD-eCB) et des voies de signalisation dépendantes du système eCB au niveau du CPF (Lafourcade et al., 2011 ; Larrieu et al, 2012). Nos données indiquent que ces altérations sont dues à un découplage entre le récepteur cannabinoïde 1 (CB1R) et la protéine Gi/o. De plus, les souris déficientes en AGPI n-3 présentent des déficits comportementaux dans plusieurs tests évaluant les comportements émotionnels. Afin de mieux comprendre les mécanismes qui sous-tendent la diminution du DHA dans le CPF et les altérations des comportements émotionnels, nous avons étudié la morphologie neuronale dans le CPF et l’axe hypothalamo-hypophysaire (HPA) chez les souris déficientes en AGPI n-3. Nous avons montré que le régime alimentaire déficient en AGPI n-3 induit une atrophie de l’arborisation dendritique dans les neurones pyramidaux du CPF. L'atrophie dendritique est semblable à celle mesurée chez les souris soumises au régime équilibré en AGPI n-3 et soumises à un stress chronique de défaite sociale (CSDS). Aucun effet additionnel du CSDS sur la morphologie neuronale et le comportement émotionnel n’a été observé chez les souris déficientes en AGPI n-3. Nous avons ensuite étudié le rôle de l’axe HPA dans le développement des altérations comportementales et neurobiologiques chez les souris déficientes en AGPI n-3. Ces souris présentent une diminution de l'expression des récepteurs des glucocorticoïdes (GR) dans le CPF associée à une augmentation des taux circulants de corticostérone. Dans leur ensemble, nos résultats montrent qu’un faible apport alimentaire en AGPI n-3 peut modifier la plasticité synaptique dépendante du système eCB ainsi que l’arborisation dendritique des neurones du CPF. Nous avons également pu montrer que l’élévation des niveaux de corticostérone était impliquée dans l’altération des comportements émotionnels observée chez des souris nourries avec un régime déficient en AGPI n-3., Low dietary intake of n-3 polyunsaturated fatty acids (PUFAs) has been associated with the prevalence of mood disorders in humans. In rodents, nutritional approaches aiming at modeling poor dietary n-3 PUFAs intake have been extensively developed in the last century. As a result, one- or multi-generation dietary n-3 deficiency induces depressive and anxiety-like behaviors. We have shown in the Nutrineuro lab that mice fed with a diet deficient in n-3 PUFAs exhibit decreased n-3 PUFAs levels, especially docosahexaenoic acid (DHA, a n-3 PUFA) levels in the prefrontal cortex (PFC) and in the nucleus accumbens (NAc). We showed that dietary n-3 PUFA is able to modulate endocannabinoid (eCB) dependent plasticity since DHA reduction in PFC and NAc is accompanied with eCB dependent long term depression (eCB-LTD) and eCB signaling impairment in the PFC (Lafourcade et al., 2011; Larrieu et al., 2012). Our data indicate that LTD alteration results from region-specific uncoupling of CB1 receptor from its effector Gi/o protein. In addition, n-3 deficient mice display behavioral deficits in several tests measuring emotional behavior. To further understand the mechanisms underlying DHA decrease in the PFC and emotional behavior alteration, we thoroughly investigated neuronal morphology and hypothalamic-pituitary-adrenal (HPA) axis in n-3 deficient mice. We showed that n-3 deficient diet induced dendritic atrophy in pyramidal neurons within the PFC. The dendritic atrophy was comparable to the one measured in control diet mice submitted to chronic social defeat stress (CSDS). No additional effect of CSDS on both neuronal morphology and emotional behavior was measured in n-3 deficient mice. We therefore investigated the role of the HPA axis deregulation in the development of behavioral and neurobiological alterations of n-3 deficient mice. We found a decreased expression of glucocorticoid receptor (GR) in the PFC of n-3 deficient mice together with increased circulating levels of corticosterone. Collectively, we unraveled one crucial mechanism underlying n-3 deficiency-induced alterations. Our results show that low dietary n-3 PUFAs can alter eCB-dependent plasticity and neuronal dendritic atrophy within the PFC leading to emotional behavior impairment. Importantly, we further demonstrated that corticosterone elevation in n-3 deficient mice was involved in the n-3 deficiency-induced emotional behavior and dendritic arborization alterations.