A whole-cell DHA-rich algal product (A-DHA, provided by Evonik Industries) that is rich in DHA (125 mg DHA/g dry matter) is a possible replacement for fish oil in salmonid diets. The nutrient digestibilities of the algal product were measured in rainbow trout in freshwater and in Atlantic salmon in saltwater (32-33 ppm). In experiment 1, rainbow trout (initial weight ~ 300g) were randomly assigned to 12 x 120 L tanks (n = 10 per tank). A reference diet containing 1% Celite as an indigestible marker and three test diets with increasing percentage of A-DHA substitution (6.67%, 13.33% and 20%) were fed. Feces were collected using a settling column and feed and feces analyzed for digestible dry matter (DM), gross energy (GE), ash, crude protein (CP), essential amino acids and total lipid. The digestibility of six long-chain fatty acids including 18:1n-9 (OA), 18:2n-6 (LA), 18:3n-3 (ALA), 20:4n-6 (ARA), 20:5n-3 (EPA) and 22:6n-3 (DHA) was measured. In experiment 2, Atlantic salmon (~170g) were randomly distributed to 12 fiberglass tanks (600L) with 106 fish per tank. The fish were assigned to four diets with the same levels of A-DHA inclusion as for rainbow trout and yttrium oxide (Y2O3) was used as an inert marker. Feces were collected by stripping and the digestibilities of DM, CP and lipid as well as OA, LA, ALA, ARA, EPA and DHA were determined. In experiment 1, the apparent digestibility of dietary DM, GE and lipid in rainbow trout declined significantly with increasing inclusion of A-DHA (P < 0.01). The inclusion of A-DHA had no effect on the digestibility of CP and ash as well as the availability of essential amino acids (P > 0.05). Furthermore, increased inclusion of A-DHA resulted in significantly lower digestibility of ARA, EPA and DHA (P < 0.05). A similar pattern was seen in the digestibility of OA, LA and ALA, although the effect of A-DHA inclusion was not statistically significant. Regression analysis revealed that nutrient contribution from A-DHA had significantly negative linear and quadratic effects on the apparent digestibility of DM, GE, and lipid. The inclusion levels of A-DHA had both significantly negative linear and quadratic effects on digestibility of LA and ALA, whereas only significantly negative linear effect was found on OA. Significantly negative linear and quadratic regressions were observed for the digestibility of ARA, EPA and DHA. The linear regression for CP was significantly negative and the regressions for the individual amino acids were not significant (P > 0.05). In experiment 2, dietary inclusion of A-DHA had a significantly negative effect on lipid digestibility in Atlantic salmon, at all inclusion rates whereas the significant negative effect on digestibilities of DM and CP was only observed in fish fed 20% A-DHA. The digestibilities of OA, LA, ALA and EPA were greater than 91%. In contrast, the apparent digestibilities of ARA and DHA decreased significantly with increasing substitution of A-DHA (P < 0.01). Significantly negative linear and quadratic regressions were found between nutrient contribution from A-DHA to the diets and apparent digestibility of DM, CP and lipid, so were LA, EPA and DHA. However, there were only significant quadratic regressions for OA, ALA and ARA, but not significant linear effects. Subsequently, a twelve-week feeding trial in rainbow trout was conducted to investigate the impact of replacing fish oil with A-DHA in canola-oil-based diets on the growth performance and fatty acid composition and retention. Four experimental diets containing only canola oil (CO; 13.5%), fish oil (FO; 13.5%), canola oil and fish oil (C+F; 7.4% and 6.1%, respectively) or canola oil and A-DHA (C+A; 15.5% and 6%, respectively) were formulated to contain 386.2 g/kg digestible crude protein and 17.58 MJ/kg digestible energy. In addition, the C+A diet was formulated to have the same DHA concentration as in the C+F diet. Each diet was fed to three tanks of rainbow trout (average initial weight of 70g; n = 17/tank) and the fish were fed to apparent satiation 2 times daily. At the end of the growth trial, all fish approximately tripled their weight. No significant differences were noted between the dietary treatments in growth performance as measured by final weight, average weight gain, feed intake, specific growth rate (SGR) and feed conversion ratio (FCR). Although FO and C+A fed fish tended to accumulate more lipids, final whole body lipid content did not differ significantly between dietary treatments (P = 0.11). The concentrations of EPA, DHA as well as total n-3 fatty acid were significantly higher in fish fed the FO diet than fish fed the other 3 diets. The C+A fed fish had lower EPA and higher DHA concentrations compared with the CO and C+F fed fish; however, the differences were not significant. Apparent retention of total lipid in the trout was not significantly influenced by treatments (P > 0.05). Similarly, dietary treatments had no significant effect on the apparent retention of total saturated fatty acids, total mono-unsaturated fatty acids, n-3 polyunsaturated fatty acids and n-6 polyunsaturated fatty acids. The retention of 18:4n-3 (SDA) was significantly higher (> 100%) in fish fed CO and C+A compared with fish fed FO and C+F (< 51%), indicating greater bioconversion of ALA to SDA in the CO and C+A fed fish than in FO and C+F fed fish. The retention of EPA in the CO and C+A fed fish was over 100%, suggesting a net synthesis of EPA in these treatment groups. In contrast, the EPA retention in the FO and C+F fed fish was 55 and 21%, respectively, which showed a tendency to be significantly lower than that in the other two groups (P = 0.09). The CO fed fish had significantly higher DHA retention than fish fed the other 3 diets. The DHA retention in the FO fed fish (112%) was numerically but not significantly higher than in the C+F (66%) and C+A fed fish (73%). Thus, feeding the C+A to rainbow trout resulted in DHA retention equal to feeding the C+F.

La résistance des cellules cancéreuses à la chimiothérapie est une cause majeure de l’échec thérapeutique. Des études suggèrent qu’une adaptation du métabolisme énergétique pourrait jouer un rôle dans cette résistance. Ce travail de thèse montre que la résistance des cellules cancéreuses mammaires MCF-7dox à la doxorubicine est associée à une diminution de l’activité du complexe I de la chaîne respiratoire mitochondriale et à un métabolisme des cardiolipines (CL) particulier (diminution de la quantité de CL et augmentation de la quantité de MLCL, la forme immature des CL). Nos résultats montrent aussi que les mitochondries des cellules MCF-7dox expriment deux pompes d’efflux ATP-dépendantes (BCRP et MRP1) qui participent à limiter la quantité de doxorubicine accumulée dans ces mitochondries. De plus, l’activité de ces deux transporteurs dépend partiellement de l’ATP mitochondrial dont l’efficacité de synthèse est améliorée dans les cellules MCF-7dox. D’autre part, nous montrons que l’effet sensibilisant du DHA à la doxorubicine dans les cellules MCF-7dox implique un stress oxydant mitochondrial et s’accompagne d’une diminution de l’efficacité de la synthèse d’ATP. / Resistance of cancer cells to chemotherapy is a major cause of treatment failure. Studies have suggested that an adaptation of energy metabolism may play a role in the development of this resistance. The present work shows that resistance of the breast cancer cell line MCF-7dox to doxorubicin is associated with decreased activity of the mitochondrial respiratory chain complex I and particularly altered cardiolipin (CL) metabolism, (decreased CL levels and increased MLCL levels, the immature form of the CL). Our results also show that mitochondria from MCF-7dox cells express two ATP-dependent efflux pumps (BCRP and MRP1) limiting the accumulation of doxorubicin in these mitochondria. In addition, the activity of these two transporters is partially dependent on mitochondrial ATP synthesis which efficiency is improved in MCF-7dox cells. Moreover, we show that the sensitizing effect of DHA to doxorubicin in MCF-7dox cells is regulated by mitochondrial oxidative stress and is accompanied by a decrease in ATP synthesis efficiency.

Foram utilizadas 168 galinhas poedeiras Hisex White em delineamento experimental inteiramente casualizado, com duração de cinco semanas. As aves foram distribuídas em sete tratamentos com três repetições cada, com o objetivo de verificar a influência da suplementação de três fontes marinhas de PUFAs n-3 - óleos de salmão (SA) e de atum e sardinha (A/S) e mistura de algas marinhas (AL), bem como sua combinações (SA+A/S, AL+SA, AL+A/S) - em relação ao grupo controle alimentado com ração basal de milho e soja (CON), sobre a qualidade do ovo e a composição lipídica da gema. A qualidade externa e interna do ovo não foi alterada significativamente pela adição de fontes de PUFAs n-3 na dieta das aves. A relação entre os lípides saturados : monoinsturados : poliinsaturados da gema (3,5 : 4,5 : 2,0) manteve-se constante com a adição dos suplementos de PUFAs n-3 na ração. Os óleos de salmão (SA) e de atum e sardinha (A/S) revelaram-se mais efetivos no enriquecimento da gema do ovo em PUFAs n-3, em especial o DHA. A relação PUFAs n-6/ PUFAs n-3 sofreu redução significativa com a adição das fontes marinhas de ômega-3 à dieta das galinhas. O EPA, embora em teores mais baixos que o DHA na gema do ovo, apresentou incremento significativo com o uso dos óleos de peixes (SA e A/S) adicionado à dieta em relação ao CON. O consumo de dois ovos enriquecidos com DHA do presente estudo, por dia, provavelmente atenderia os requerimentos diários deste PUFA n-3 para o ser humano / To investigate the influence of three PUFAs n-3 marine sources - salmon oil (SA), tuna and sardine oil (A/S), marine algae (AL) and combinations (SA+A/S, AL+SA, AL+A/S) - on egg quality and egg lipid composition, compared to a corn/soy control group (CON), 168 Hisex White laying hens were assigned into seven treatments with three repetitions in a randomized design during a experimental period of five weeks. The external and internal egg quality were not significantly affected by the addition of PUFAs n-3 marine sources into the hen diets. The saturated : monounsaturated : polyunsaturated ratio (3.5:4.5:2.0) remained constant by the supplementation of the marine sources into the diets. The salmon oil and the tuna and sardine oil showed the best results of PUFAs n-3 egg yolk enrichment, mainly the DHA. The PUFAs n-6/PUFAs n-3 ratio was significantly reduced by the inclusion of PUFAs n-3 sources into the hen diets. The EPA, although with lower levels than DHA into the egg yolk, showed a significant increase by the use of salmon oil and tuna and sardine oil added to the diet as compared to the control group (CON). The consumption of two DHA enriched eggs from this study per day probably would reach the daily requirements of this PUFA n-3 for the human been

Alimentos e suplementos adicionados de ácidos graxos poliinsaturados ômega 3, tais como os ácidos eicosapentaenóico (EPA) e docosaexaenóico (DHA), tem sido comercializados com a alegação funcional de reduzir as concentrações de triacilgliceróis (TG) e, assim, reduzir o risco para doenças cardiovasculares. Entretanto, pelo fato desses ácidos graxos apresentarem uma cadeia carbônica altamente insaturada, o consumo crônico em doses elevadas poderia levar a um aumento da susceptibilidade do organismo ao estresse oxidativo. O desequilíbrio nos processos oxidativos pode ser um agravante em indivíduos dislipidêmicos, uma vez que essa população normalmente controla as altas concentrações de lipoproteína de baixa densidade (LDL) com medicamentos como as estatinas, e a oxidação da LDL é um dos fatores mais importantes para o desenvolvimento da aterosclerose. Uma vez que a proposta dos alimentos funcionais e suplementos nutracêuticos é de agir como coadjuvantes à prescrição terapêutica, indivíduos sob tratamento a base de estatinas seriam um público-alvo para produtos adicionados de ácidos graxos ômega 3. Desta forma, a proposta deste estudo foi de avaliar o efeito de uma suplementação contendo EPA e DHA sobre alguns biomarcadores do estresse oxidativo em mulheres com dislipidemia controlada por estatinas. Seguindo delineamento crossover duplo cego, 45 indivíduos foram distribuídos em 4 grupos e receberam a seguinte suplementação: cápsulas de óleo de milho/soja, sem estatina (Placebo); cápsulas de milho/soja, com estatina (Estatina); cápsulas de óleo de peixe, sem estatina (Omega 3); cápsulas de óleo de peixe, com estatina (Combinado). Os indivíduos foram orientados a consumir 4 cápsulas (2,3 g de EPA e DHA) por dia durante 42 dias. Foram realizadas coletas de sangue antes e após o período de intervenção para analise das concentrações séricas de glicose, lipoproteínas, perfil de ácidos graxos no plasma e marcadores do estresse oxidativo. A suplementação com EPA e DHA na dosagem de 2,3 g/dia foi efetiva na redução das concentrações séricas de LDL e TG apenas na presença de estatinas, confirmando o uso combinado desses compostos para melhoria do perfil lipoprotéico. Por outro lado, essa suplementação parece induzir um aumento do estresse oxidativo, evidenciado pelo aumento da concentração plasmática de malondialdeído, provavelmente decorrente da redução da expressão da catalase promovida pelos AGPI n-3. / Food and supplements that contain n-3 fatty acids, such as eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids, have been commercialized using functional claim to reduce triacylglycerol (TG) concentration and, hence, reduce the risk of cardiovascular diseases. However, as these fatty acids are highly unsaturated, the chronic consumption in high doses could raise the susceptibility of the organism to oxidative stress. Oxidative processes imbalance can be a problem in dyslipidemic individuals, once this population usually controls the high concentration of low density lipoproteins (LDL) with drugs such as statins, and oxidation of LDL is one of the most important factors to the atherosclerosis development. Since functional foods and nutraceutical supplements are supposed to contribute to the therapeutic prescription, dyslipidemic individual under statins treatment could be the target to products containing n-3 fatty acids. Thus, the objective of this study was to evaluate the effect of a supplementation containing EPA and DHA on some biomarkers of oxidative stress in women with dyslipidemia controlled by statins. A randomized double-blind placebo-controlled crossover study was carried out with 45 women who were distributed into 4 groups that received the following supplementation: corn/soy oil capsules, no statin (Placebo); corn/soy oil capsules, with statin (Statin); fish oil capsules, no statin (Omega 3); fish oil capsules, with statin (Combined). The individuals were instructed to consume 4 capsules (2.3 g of EPA and DHA) every day during 42 days. Blood samples were collected before and after the supplementation to evaluate serum glucose and lipoprotein concentrations, plasma fatty acid profile and biomarkers of oxidative stress. N-3 PUFA supplementation (2.3 g/day) was effective in reducing serum LDL and TG concentrations only when combined with statins, confirming the combined use of these compounds for improvement of lipoprotein profile. On the other hand, this supplementation seemed to induce an increase of the oxidative stress, evidenced by the higher malondialdehyde plasma concentrations, probably due to the reduction in catalase expression promoted by n-3 PUFA.

Parmi les œufs de poisson, qui sont une ressource aquatique nutritionnelle intéressante, ceux de la truite arc-en-ciel (Oncorhynchus mykiss) contiennent une quantité élevée de protéines et une huile riche en acides gras polyinsaturés (AGPI), avec une proportion très importante de phospholipides. Cependant, l’œuf de poisson présente une capacité élevée d’auto-protection contre les contraintes extérieures, qui limite la destructuration de son réseau protéique par attaque enzymatique. Ainsi, le degré d’hydrolyse des œufs de la truite l’Alcalase®, la Neutrase® et la Protamex® varie entre 3 et 7 %, ce qui est très faible (20 % dans la majorité des protéines animales). L’extraction des lipides après protéolyse partielle est incomplète, probablement en raison d’interactions fortes avec les protéines faiblement hydrolysées. Ils contiennent une teneur élevée en phospholipides (53 % des lipides totaux) et les acides gras polyinsaturés entrent pour 42 % des acides gras totaux. Les AGPI, notamment le DHA, sont situés préférentiellement en position sn-2 sur la molécule de glycérol ce qui est particulièrement intéressant du point de vue nutritionnel. La stabilité à l’oxydation de l’huile a été étudiée par diverses méthodes, dont la spectrométrie infrarouge à transformée de Fourier. Cette méthode s’est avérée extrêmement intéressante pour une analyse structurale de la dégradation de l’huile en cours d’oxydation. Il peut être conclu que les lipides tirés des œufs de la truite arc-en-ciel ou de poisson en général, ont un réel avenir en matière de complément alimentaire ou nutraceutique, à condition de lever l’obstacle de l’hydrolyse enzymatique des protéines du chorion et du vitellus / Fish eggs, especially those of the rainbow trout (Oncorhynchus mykiss) in the present study, are an interesting nutritional aquatic source. They contain proteins of high value, as well as an oil rich in polyunsaturated fatty acids (PUFA) with a large percentage of phospholipids. However, they exhibit a high auto-protection capacity against environmental constraints and thus, the degree of hydrolysis of rainbow trout eggs by Alcalase®, Neutrase® and Protamex® proteases varied solely within 3-7 %. This value was low compared with the 20 % obtained in most animal proteins. The phospholipid content was high (53 % of total lipids) and PUFA accounted for 42 % of total fatty acids. Among PUFA, DHA was found preferably at the sn-2 position of the glycerol backbone, which is of special interest about nutritional properties. The oil release by enzymatic hydrolysis was found limited compared with chemical methods, probably because of the strong interactions engaged with the incomplete destructured protein network. The oxidative stability of the oil was studied through several methods in which the infrared Fourier transform appeared as the best tool for structural analysis along the oxidation process. As a conclusion, lipids from fish eggs, especially from rainbow trout, could be a nutritional breakthrough, as far the enzymatic hydrolysis of the vitellus and of the chorion proteins is achieved

Avaliamos no presente estudo: 1) os efeitos do desuso das patas traseiras de ratos por duas semanas sobre as vias de sinalização de síntese e degradação de proteínas no músculo sóleo e a administração de óleos de peixe ricos em eicosapentaenóico (EPA) ou docosaexaenóico (DHA) e 2) as alterações induzidas pelo desuso no músculo sóleo em camundongos FAT-1. Concluímos que, apesar da variação pequena na razão ácidos graxos ômega-6/ômega-3, efeitos significativos da oferta aumentada de ácidos graxos ômega-3 foram observados na área de seção transversa e vias de sinalização relacionadas à síntese e degradação de proteínas no músculo sóleo nos dois protocolos. / We investigated herein: 1) the effects skeletal muscle disuse atrophy induced by two-week hind limb suspension (HS) on protein synthesis and degradation signaling in soleus muscle and the administration of either eicosapentaenoic (EPA) or docosahexaenoic (DHA)-rich fish oil supplementation, and 2) the changes induced by hind limb disuse on soleus muscle of Fat-1 transgenic mice. We concluded that, in spite of the small variation in the omega-6/omega-3 fatty acid ratio, significant effects of the increased omega-3 fatty acid levels were observed on the CSA and signaling pathways associated with soleus muscle protein synthesis and degradation in both experimental protocols.

O diabetes mellitus tipo I (DMI) é uma doença crônica autoimune caracterizada por hiperglicemia devido à destruição das células beta pancreáticas produtoras de insulina. Ao final de 30 dias da indução do diabetes por estreptozotocina, os macrófagos peritoneais residentes dos animais diabéticos apresentaram aumento de RNAm de citocinas e quimiocinas inflamatórias, secreção de óxido nítrico, expressão de NLRP3, iNOS e PARP1 e da atividade da via glicolítica. Perfil pró-inflamatório também foi observado em macrófagos peritoneais de animais NOD (non-obese diabetic). Camundongos diabéticos deficientes em NLRP3 (NLRP3 KO) apresentaram diminuição na expressão de iNOS, PARP1 e na produção de NO em relação aos macrófagos dos animais diabéticos selvagens. O estado diabético tipo I influenciou o perfil dos macrófagos peritoneais residentes, causando aumento na produção de NO, via NLRP3-PARP1-iNOS, expressão de citocinas pró-inflamatórias, receptores de quimiocinas e da atividade glicolítica. O tratamento com DHA (ômega-3) ex-vivo reverteu este perfil e atenuou o quadro pró-inflamatório por diminuição da produção de NO e da expressão de citocinas pró-inflamatórias. / Type I diabetes mellitus (DMI) is a chronic autoimmune disease characterized by hyperglycemia due to the destruction of insulin-producing pancreatic beta cells. At the end of 30 days after type I diabetes induced by streptozotocin, macrophages from diabetic animals had increased expressions of inflammatory cytokines and chemokines, secretion of nitric oxide, expression of NLRP3, iNOS and PARP1, and glycolytic activity compared to the cells from control animals. Proinflammatory features was also observed in peritoneal macrophages of NOD (non-obese diabetic) animals. Macrophages from NLRP3 deficient diabetic mice (NLRP3 KO) had decreased expression of iNOS, PARP1 and of NO production when compared to cells from wild type animals. The type I diabetic state led to a proinflammatory feature in resident peritoneal macrophages by increasing NO production, via the NLRP3-PARP1-iNOS pathway, expressions of proinflammatory cytokines, chemokine receptors and glycolytic activity. In contrast, ex-vivo treatment with DHA (omega-3) reversed this profile and attenuated the proinflammatory state by reducing NO production and expression of proinflammatory cytokines.

The advertisement of menstrual products has traditionally been characterised by shame, discretion and euphemisms (Block Coutts and Berg 1993; Waschek 1995, Simes and Berg 2001). In the past few years, the theme of menstruation appears increasingly in the public eye and prompts the question of whether those qualities are still the dominant descriptors for advertising menstrual products. In order to study this, a critical discourse analysis was performed using the discourse-historical approach of Wodak and Reisigl (2016). The intention was to investigate – both qualitatively and quantitatively – how product descriptions of pads, tampons and menstrual cups are normatively and predicatively constructed, and which arguments, linguistics means and realizations are utilized for this purpose. The results suggest that qualities such as cleanliness, discretion and absence of smell as well as euphemisms (e.g. Flüssigkeit, leichte/stärkere Tage) are still quite prevalent in use. The focus on protection is also emphasized in various ways, both in the product names as well as in the frequency analysis of the adjoining texts. However, other qualities, such as comfort, indicate that progressive tendencies also exist in the advertisements of menstrual products.

Der globale Prävalenzanstieg allergischer Erkrankungen wird mit der westlichen Ernährung und einem sich ändernden Fettsäurespektrum assoziiert. Die omega-3 Fettsäure Docosahexaensäure (DHA) wurde bereits bei verschiedenen chronisch-entzündlichen Erkrankungen erfolgreich therapeutisch eingesetzt. Die dabei zugrunde liegenden Wirkmechanismen sind jedoch nicht vollständig geklärt. Deshalb wurde hier der molekulare Mechanismus der DHA-vermittelten Hemmung der IgE-Produktion in humanen B-Zellen sowie der verminderten Differenzierung IgE-produzierender Plasmazellen in vitro untersucht. Analysen der beteiligten Signaltransduktionswege offenbarten eine Reduktion der IL-4-abhängigen STAT6-Phosphorylierung und der CD40-vermittelten NFkappaB-Translokation, was zu einer Inhibition des IgE-Klassenwechsels auf dem Niveau des epsilon-Keimbahntranskriptes sowie der Aktivierungsinduzierten Desaminase führte. Weiterhin wurde in einer randomisierten, kontrollierten Doppelblindstudie die Supplementierung mit hochdosierter DHA bei Patienten mit atopischem Ekzem hinsichtlich klinischer und immunologischer Parameter geprüft. Dabei führte DHA zu einer Reduktion des Schweregrades der Erkrankung und zu einer verminderten IgE-Produktion anti-CD40/IL 4-stimulierter Blutzellen ohne Beeinflussung des Serum-IgE-Spiegels. Schließlich wurden die lokalen Prozesse nach DHA-Verabreichung in einem Mausmodell für proteininduzierte Dermatitis analysiert. Dabei war die Reduktion der klinischen Ekzemausprägung mit der verminderten Zahl dermaler CD8+ T-Zellen verbunden. Andere histologische Parameter und das Serum-IgE blieben jedoch unbeeinflusst. Durch die Fähigkeit von DHA, in den IgE-Klassenwechsel in B-Zellen einzugreifen, stellt die Supplementierung mit DHA somit eine mögliche präventive Maßnahme gegen allergische Erkrankungen dar. Ebenso ist DHA in der Lage, den Schweregrad des atopischen Ekzems durch die positive Beeinflussung lokaler inflammatorischer Prozesse signifikant zu verbessern. / The prevalence of allergic diseases has increased worldwide. Westernised diet with its changing polyunsaturated fatty acid (PUFA) proportions is considered to contribute to this development. The omega-3 PUFA Docosahexaenoic acid (DHA) has been reported to be antiinflammatory, but its way of action is not completely understood. Initially, the molecular mechanisms of DHA impact on IgE production in human B cells were examined in vitro. Thereby, DHA inhibited IgE production and the differentiation of IgE secreting cells. This was mediated through direct inhibition of the immunoglobulin isotype switching process by decreasing epsilon germline transcript and activation induced desaminase transcription. Analysis of involved signalling pathways revealed an inhibition of IL-4 driven STAT6 phosphorylation and a reduced NFkappaB translocation into nucleus upon CD40 ligation. Next, in a randomised, double bind, controlled clinical study the efficacy of high-dose DHA supplementation in atopic eczema was determined by investigating the impact on clinical and immunological parameters. In the DHA, but not in control group a clinical improvement of atopic eczema and a reduction of CD40/IL-4 mediated IgE synthesis of peripheral blood cells were observed whereas serum IgE levels remained unchanged. Finally, in a mouse model the impact of oral DHA application on allergen induced dermatitis as well as the underlying local mechanisms were investigated. Thereby, the DHA mediated reduction of clinical skin score was associated with decreased dermal CD8+ T cell numbers, whereas other histological parameters or serum IgE values were not affected. In summary the results indicate that dietary DHA may be effective in prevention of allergic diseases by interference with the IgE switching process and improve the clinical outcome of atopic eczema by its positive impact on local inflammatory processes.

La qualité des lipides des préparations pour nourrissons est primordiale, notamment en termes d’acides gras polyinsaturés (AGPI) comme l’acide arachidonique (ARA) et docosahexaénoïque (DHA). Ces derniers pourraient favoriser le développement neurosensoriel de l’enfant. Nous avons ainsi évalué 4 standards commerciaux contenant des lipides végétaux ou laitiers et supplémentés ou non en ARA/DHA, sur le développement neurosensoriel au travers d’un modèle d’allaitement artificiel « pups in the cups ». En TEP-cs, nous observons que la supplémentation en ARA/DHA permet de normaliser le fonctionnement cérébral.L’exploration des lipides tissulaires indique des différences en DHA particulièrement bas avec l’allaitement en lipides végétaux purs. Nous proposons un algorithme de prédiction du DHA cérébrale et oculaire via les profils en acides gras érythrocytaires. Dans ces tissus un tiers des espèces à DHA sont affectées et corrélées à l’activité cérébrale. Les neuromédiateurs issus de l’AL, ARA, DHA par la voie LOX sont impactés ainsi que la distribution spatiale en DHA en IMS. Les autres données omiques soulignaient l’impact des interactions fond lipidique x ajout DHA/ARA (transcriptomique) ou fond lipidique (métabolomique) sur la régulation du métabolisme cérébral impactant le métabolisme neuronal et le métabolisme cérébral du microbiote probablement via l’axe de signalisation intestin-cerveau. Nous identifions alors un métagénome sensible à l’ajout DHA/ARA corrélé à la fonction cérébrale. Enfin, des modifications épigénétiques (méthylation du génome et miARN) touchant le groupe FC suggèrent potentiellement un impact à long terme. / The quality of lipids in infant formula is essential, especially in terms of polyunsaturated fatty acids (PUFAs) such as arachidonic acid (ARA) and docosahexaenoic acid (DHA). These could promote the neurosensory development of the child. We thus evaluated 4 commercial standards containing plant or dairy lipids and supplemented or not with ARA / DHA, on the neurosensory development through an artificially feeding model "pups in the cups". In PET-cs, we observe that the supplementation in ARA / DHA makes it possible to normalize the cerebral functioning. The exploration of tissue lipids indicates differences in DHA which are particularly low with pure plant lipids intake. We propose an algorithm for predicting cerebral and ocular DHA via erythrocyte fatty acids profiles. In these tissues one-third of the DHA species are affected and correlated with brain activity. The neuromediators resulting from AL, ARA, DHA by the LOX pathway are impacted as well as the spatial distribution of DHA in IMS imaging. Other omics data underlined the impact of lipid background x combination DHA / ARA (transcriptomics) or lipid background (metabolomics) on the regulation of cerebral metabolism impacting neuronal metabolism and brain metabolism of the microbiota probably through the signalling of gut-brain axis. We then identify a metagenome sensitive to the addition of DHA / ARA correlated to brain function. Finally, epigenetic modifications (methylation of the genome and miRNA) affecting the FC group potentially suggest a long-term impact.