A oviposição é um estágio vulnerável do ciclo de vida de carrapatos. Rhipicephalus microplus, como todos Ixodidae e Argasidae, possui uma glândula especializada, o órgão de Gené, que produz uma cera que é depositada na superfície do ovo durante a oviposição. Além de restringir a perda excessiva de água, a cera atua como uma barreira contra o ataque de organismos invasores. Em R.microplus, como em outros carrapatos, há poucos estudos demonstrando atividade antimicrobiana em ovos. Ainda mais, não há na literatura relato de atividade antibiofilme em ovos de carrapatos e nem mesmo em qualquer outro artrópode. O objetivo do presente trabalho foi avaliar a hipótese da existência de mecanismos de defesa em ovos de R. microplus contra biofilmes bacterianos. O extrato água/metanol da cera dos ovos apresentou atividade contra o biofilme de Pseudomonas aeruginosa sem afetar a sua viabilidade. Esse extrato também demonstrou efeito antibiótico contra Staphylococcus epidermidis. Nós identificamos a molécula com ambas atividades (antibiofilme e antibiótica) como N-(3-sulfooxy-25-cholest-5-en-26-oyl)-L-isoleucina (boophiline). Na busca por possíveis mecanismos responsáveis pelo efeito antibiofilme de boophiline contra P. aeruginosa, 14 genes foram analisados por qRT-PCR. Boophiline inibe a expressão de fliC (flagelo) e cdrA (componente estrutural da matriz), cujos produtos são necessários para a formação do biofilme de P. aeruginosa. Monosfosfato de guanosina dimérico cíclico (c-di-GMP) é um importante segundo mensageiro característico de bactérias Gram-negativas. Altos níveis intracelulares de c-di-GMP promovem o estilo de vida séssil enquanto baixos níveis induzem o comportamento móvel. De acordo com essa afirmação, nós encontramos que boophiline aumenta a motilidade swarming de P. aeruginosa. Desta forma, nos questionamos se o mecanismo de ação de boophiline estaria envolvido com c-di-GMP já que o sistema quorum sensing não foi afetado pela molécula. Interessantemente, quando os níveis de c-di-GMP foram aumentados pela superexpressão de uma diguanilato ciclase, boophiline não inibiu efetivamente a formação de biofilme. Uma explicação para esse resultado é que boophiline interfere em uma via específica regulada por c-di-GMP, o que explicaria não termos obtido um decréscimo no nível total deste segundo mensageiro. Contrariamente, boophiline foi bactericida contra S. epidermidis. Mudanças morfológicas significativas foram observadas em células tratadas com a molécula, as quais foram severamente danificadas. Boophiline levou a formação anormal de septo, rompimento da membrana bacteriana e extravasamento do material intracelular. Adicionalmente avaliamos o potencial antibiofilme e anti-protozoário de filtrados de cultura obtidos de bactérias isoladas de tecidos de R. microplus. Quatorze filtrados de cultura bacteriano apresentaram notável atividade contra o biofilme de P. aeruginosa e S. epidermidis e foram citotóxicos contra Tritrichomonas foetus. Nosso trabalho é pioneiro em demonstrar a existência de proteção contra biofilmes em ovos de carrapatos bem como de bactérias associadas a carrapatos como produtoras de moléculas bioativas. Além disso, nós demonstramos que boophiline é uma nova molécula antibiofilme, sendo a primeira vez relatado na literatura que um composto age inibindo cdrA. Os dados obtidos em nosso estudo poderiam estimular novas abordagens em áreas como fisiologia e controle de artrópodes, genética e fisiologia de microrganismos e controle de biofilmes. / The oviposition is a vulnerable stage of the tick life cycle. Rhipicephalus microplus, as all Ixodidae and Argasidae, has a specialized gland, the Gene’s organ, which produce a wax that is smeared on egg surface during oviposition. In addition to restricting excessive water loss, wax acts as a barrier to attack by invading organisms. In R. microplus, as in other ticks, there are few studies showing antimicrobial activity in eggs. Moreover, there is no report of antibiofilm activity in tick eggs nor in any other arthropod. The objective of our study was to evaluate the hypothesis of the existence of defense mechanisms against bacterial biofilms in R. microplus eggs. The eggs wax water/methanol extract showed activity against Pseudomonas aeruginosa biofilm without affecting its viability. This extract also presented an antibiotic effect against Staphylococcus epidermidis. We have identified the molecule anti-biofilm and antibiotic as N-(3-sulfooxy-25-cholest-5-en-26-oyl)-L-isoleucine (boophiline). In the search for possible mechanisms responsible by antibiofilm effect of boophiline against P. aeruginosa, 14 genes were evaluated by qRT-PCR. We showed that boophiline inhibits the expression of fliC (flagellum) and cdrA (matrix structural component), whose products are necessary for biofilm formation in P. aeruginosa. Bis-(3’–5’)-cyclic dimeric guanosine monophosphate (c-di-GMP) is an important second messenger, characteristic of Gram-negative bacteria. High intracellular levels of c-di-GMP promote a sessile mode of growth, while low levels promote motile behavior. In line with this, we found that boophiline increases swarming motility, which raised the question whether it acts by altering c-di-GMP levels. Interestingly, when c-di-GMP levels were increased by overexpression of a diguanilate cyclase, boophiline no longer inhibited biofilm formation. One explanation for these results is that boophiline interferes with a specific c-di-GMP-regulated pathway, which would explain we have not obtained a decrease in the total level of this second messenger. Conversely, boophiline had a bactericidal effect against S. epidermidis. Significant morphological changes were observed in the boophiline-treated cells, which appeared to be severely damaged. Boophiline was found to cause abnormal septum formation, bacterial membrane disruption, and extravasation of intracellular material. Additionally, our work also aimed to evaluate the potential antibiofilm and anti-protozoa of culture filtrates obtained from bacteria isolated of R. microplus tissues. Fourteen bacterial culture filtrates showed remarkable activity against of P. aeruginosa and S. epidermidis biofilms, and were cytotoxic against Tritrichomonas foetus. Our work is pioneer in demonstrating the existence of protection mechanisms in tick eggs against biofilms, and ticks-associated bacteria as producers of bioactive molecules. Furthermore, we demonstrated that boophiline is a new antibiofilm molecule, and is the first reported in the literature that a molecule inhibits cdrA. The data obtained in our study could stimulate new approaches in areas such as the physiology and control of arthropods, the genetics and physiology of microorganisms, and biofilm control.

L’obésité est une maladie associée à des altérations métaboliques et inflammatoires et constitue un facteur de risque important de développer des comorbidités telles qu’un diabète de type 2. De plus, la prévalence de troubles de l’humeur et de la cognition est élevée chez les sujets obèses. Ces troubles neuropsychiatriques compliquent la prise en charge de l’obésité, contribuent à son aggravation et peuvent à terme favoriser le développement des comorbidités associées. Diminuer le développement de ces troubles pourrait donc permettre d’améliorer la santé et la qualité de vie des individus obèses. Dans ce contexte, l’objectif de cette thèse a été de comprendre les mécanismes neurobiologiques sous-tendant l’apparition de ces troubles neuropsychiatriques, dans le but d’identifier de nouvelles cibles potentielles pour le développement de stratégies préventives et/ou thérapeutiques visant à les réduire. Dans ce but, des modèles animaux d’obésité tels que la souris db/db, qui présentent une obésité sévère associée à des altérations caractéristiques du syndrome métabolique, peuvent être particulièrement utiles.[ ]Dans un premier temps, nous avons montré qu’une restriction calorique ou un traitement anti-inflammatoire diminuait les comportements de type anxieux chez la souris db/db. Cette amélioration était associée à une diminution sélective de l’expression génique du TNF-α dans l’hippocampe, ce qui suggère une contribution de cette cytokine pro-inflammatoire dans les comportements de type anxieux associés à l’obésité. Nous avons ensuite confirmé cette hypothèse en montrant que le blocage sélectif du TNF-α cérébral par administration i.c.v. d’étanercept (un récepteur leurre du TNF-α) diminuait les comportements de type anxieux chez les souris db/db. De façon intéressante, des mesures électrophysiologiques ont permis de montrer que cette amélioration des comportements émotionnels par l’étanercept impliquait la modulation de l’activité spontanée des neurones dans l’hippocampe ventral, région connue pour son rôle dans la régulation des émotions. Dans un second temps, nous avons essayé d’identifier de nouvelles stratégies préventives et/ou thérapeutiques pour améliorer l’humeur et la cognition chez les sujets obèses. Nous avons donc évalué l’effet d’un régime enrichi en acides gras polyinsaturés de type n-3 et antioxydants sur les altérations comportementales des souris db/db. En effet, ces nutriments sont connus pour moduler différents paramètres neurobiologiques impliqués dans la régulation du comportement. Nous avons montré que la consommation chronique de ce régime supprimait les déficits de mémoire spatiale dépendante de l’hippocampe chez les souris db/db dans le test de la piscine de Morris et que cette amélioration cognitive était probablement sous-tendue par des changements de plasticité neuronale. Enfin, nous avons évalué si des manipulations du microbiote intestinal pouvaient représenter une stratégie préventive et/ou thérapeutique pour améliorer les altérations neuropsychiatriques associées à l’obésité. Nous avons donc mesuré l’impact d’une manipulation du microbiote intestinal par des prébiotiques sur les altérations métaboliques et comportementales des souris db/db, mais également sur les systèmes biologiques et neurobiologiques auxquels elles sont associées. Nous avons montré que les améliorations métaboliques induites par l’administration de prébiotiques chez la souris db/db étaient accompagnées d’une diminution de l’inflammation périphérique et centrale. [ ] Pour conclure, ces expériences contribuent à montrer que l’inflammation, en particulier le TNF-α, pourrait être une cible importante pour le développement de traitements visant à améliorer les troubles de l’humeur chez les sujets obèses ; alors que des interventions nutritionnelles avec des nutriments d’intérêt pourrait plutôt aider à protéger des altérations métaboliques et/ou cognitives chez ces patients. / Obesity is a metabolic and inflammatory disorder that represents a major risk factor for the development of comorbidities such as type 2 diabetes. Obese patients also often experience mood and cognitive dysfunctions that represent important risk factors for aggravation of obesity and related outcomes. Reducing the development of such alterations may therefore allow improving health and quality of life of obese subjects. In this context, this thesis aimed to decipher the neurobiological mechanisms underlying such neuropsychiatric alterations, in order to identify new targets for the development of potential preventive and/or therapeutic strategies aiming to reduce these alterations. To do so, rodent models of obesity such as the db/db mice, which display severe obesity associated with classical features of metabolic syndrome, can be particularly useful.[ ] Second, we have investigated whether a nutritional intervention with n-3 polyunsaturated fatty acids (n-3 PUFAs) and antioxidants, which are well-known to display anti-inflammatory and neuroprotective properties, improved obesity-associated neuropsychiatric alterations. In addition, we have measured the consequences of chronic administration of the prebiotic oligofructose on the behavioral alterations displayed by db/db mice since previous studies pointed to the gut microbiota as an important player in the regulation of behavior. Finally, we have investigated the potential underlying mechanisms by measuring the impact of this treatment on the metabolism and systemic inflammation, but also on neurobiological systems known to be involved in the control of food intake and behavior. We first showed that an anti-inflammatory treatment or caloric restriction reduced anxiety-like behaviors, and this was associated with a selective decrease of hippocampal TNF-α mRNA expression, suggesting that this pro-inflammatory cytokine likely contributes to induce anxiety-like behavior associated with obesity. We then nicely confirmed this assumption by showing that selectively blocking brain TNF-α by chronically administrating etanercept i.c.v. (TNF-α decoy receptor) indeed decreased anxiety-like behaviors in obese db/db mice.[ ] Secondly, we tried identifying new preventive and/or therapeutic strategies aiming to improve mood and cognitive alterations associated with obesity. Hence, we measured if an n-3 polyunsaturated fatty acids/antioxidants enriched diet, well-known to modulate different neurobiological mechanisms potentially involved in behavioral alterations displayed by db/db mice, improved their behavioral alterations. We showed that chronic consumption of this diet reversed hippocampus-dependent spatial memory deficits displayed by db/db mice in a water-maze task and that this effect likely involved modulation of neuronal plasticity. Thirdly, we tested whether manipulating the gut microbiota composition may constitute a preventive and/or therapeutic strategy to improve the neuropsychiatric alterations associated with obesity. Hence, we assessed for the first time the effect of microbiota manipulation with a prebiotic on the metabolic and behavioral alterations displayed by db/db mice, but also on their systemic and neurobiological correlates. We showed that improvement of metabolic alterations following prebiotic administration in db/db mice was associated with selective reduction of peripheral and central inflammation, which is however not accompanied by detectable improvement of anxiety-like behavior or spatial memory deficits. To conclude, these experiments contribute to show that inflammation, and especially TNF-α, could be an important target to develop therapeutic treatments for mood alterations associated with obesity, whereas nutritional interventions with selective nutrients of interest may rather help preventing associated metabolic and/or cognitive alterations.

Les omégas trois ont un bénéfice prouvé dans la prévention de maladie cardiovasculaire et l’inflammation. Un apport optimal peut être réalisé avec des modifications diététiques simples permettant d’avoir un enrichissement des membranes cellulaires et un effet métabolique. Le tissu adipeux de part son rôle important dans la genèse du syndrome métabolique semble être une cible importante du traitement par oméga trois. Les patients avec une maladie rénale chronique (MRC) ont un risque cardiovasculaire accru et cumulent les perturbations métaboliques comme le syndrome métabolique et un état micro inflammatoire. Des doses supra physiologiques d’oméga trois ont été utilisés dans le passé dans des études de prévention rénale ou traitement de dyslipidémie. Or l’effet métabolique en fonction de la dose d’oméga 3 n’est pas connu. En accord, avec les études chez le sujet sain, en fonction de la dose administrée, les omégas 3 ont un impact différent métabolique et sur l’expression génique. Des études complémentaires sont nécessaires pour vérifier la faisabilité et l’impact métabolique d’une modification de régime afin de diminuer le rapport n-6/n-3, ainsi que l’effet à long terme des omégas trois chez ces patients. Par ailleurs, les mécanismes impliqués dans les différences de dose réponse devront être caractérisés sur un modèle animal / Omega 3 fatty acids play an important modulatory role in metabolic and inflammatory responses, the progression of atherosclerosis and gene expression. Recent studies suggest their beneficial impact on adipocyte morphology and function. Chronic kidney disease (CKD) patients have an increased cardiovascular morbi-mortality and suffer from a cluster of metabolic disorders. On the basis of previous studies there are reasons to suggest that omega 3 supplementation may offer a host of benefits to CKD patients. Unfortunatly, published studies on the effect of such supplementation are characterized by supra physiological omega 3 doses, that may be difficult to implement for extended periods in one hand and in the other hand the metabolic effect of different doses of omega 3 hasn’t been studied in detail. Simple dietary modifications can help achieve the recommended n-6/n-3 ratio in healthy subjects. In CKD patients supplementation with n-3 shows a differential dose response effect. Further studies are required to test the faisability and metabolic impact of dietary modifications in order to decrease n-6/n-3 ratio and to assess the long term effect of omega supplementation in CKD patients. Finally the molecular pathways implicated in this differential dose response should be assessed in animal models

The prevention and treatment of obesity is a major problem of health care systems in affluent societies. Metabolism of adipose tissue belongs to the therapeutical targets, since accumulation of adipose tissue is the basis of obesity development. Experiments using transgenic mice with ectopic expression of brown- fat uncoupling protein 1 (UCP1) in white adipose tissue (WAT), verified a concept that obesity could be ameliorated by increasing energy expenditure in WAT. The goal of the experiments of this PhD Thesis was to characterize in detail the phenotype of this unique animal model of obesity resistance. We have shown that mitochondrial uncoupling in WAT resulted in increased oxidation of fatty acids (FA), in face of decreased lipogenesis and induced mitochondrial biogenesis in this tissue. In further studies, we aimed to modulate propensity to obesity be increasing FA oxidation in WAT in response to physiological stimuli. This could be accomplished in response to the combination treatment using n-3 polyunsaturated fatty acids (n-3 PUFA) and mild calorie restriction in mice fed high-fat diet. Synergistic induction of mitochondrial oxidative capacity and lipid catabolism in epididymal WAT was associated with suppression of low-grade inflammation of WAT, which is typical for obesity. The improvement of lipid...

Dietary N-3 PUFA plays a key role in brain maturation, development, stress response and cognitive abilities (Weiser et al., 2016; Devarshi et al., 2019). As adolescent’s prefrontal cortex is maturating, the period becomes sensitive to external factors such as environment, nutrition, and stress (Petrovich et al., 2001; Calabro et al., 2020). In this thesis, we aim to expand our knowledge of the influence of external factors, such as dietary omega-3 supplementation and enriched environment, during this critical maturation period. By designing four distinct studies, we tested the hypothesis that visible sex-specific alterations would arise from adolescence targeted diet n-3 PUFA supplementation and enriched environment, which would act to modify physiological and stress responses, as well as socio-emotional and cognitive performance. Our first study characterized the impact n-3 PUFA and n-6 PUFA regimen on corticosterone secretion and behavioural responses in adolescent male rodents. Additionally, it assessed the effects of delivery method (gavage versus restricted feeding) during this sensitive maturation period to ensure using a method with limited stress-mediated outcomes. This study highlighted gavage to induce reduced effects on corticosterone (CORT) secretion, regardless of the provided supplementation. On the last day of feeding, CORT secretion was diminished in fish oil (FO) fed rats exposed to restricted feeding, suggesting FO diet to promote physiological adjustments. Data also demonstrated that FO and soybean (CSO) rich diets were able to reduce anxiety-like behaviour compared to a high-fat diet intake (Hydrogenated Vegetal Fat - HVF), highlighting the role of n-3 PUFA dietary supplementation during adolescence on stress regulation. Our second study assessed sex-specific impact of adolescence targeted dietary supplementation on brain Docosahexaenoic Acid (DHA), Arachidonic Acid (AA) and Linolenic acid (LA) concentrations immediately following supplementation and during adulthood. Our findings demonstrated overall elevated DHA, AA and LA brain tissue concentrations in female compared to male rats, regardless of dietary supplementation. Benefit of supplementation were most apparent in adolescent males, where FO led to higher DHA concentrations compared to soybean oil supplementation, supporting a positive influence of FO dietary supplementation in males during intensive hormonal fluctuation and brain maturation. However, adolescent male rats showed reduced ability to extract nutrient essential fatty acids compared to female counterparts. Our third study characterized sex-specific coping strategies, socioemotional responses, and glucocorticoid regulation following an n-3 PUFA rich diet and enriched environment (EE) during the adolescent period. While basal CORT secretions were not significantly altered by supplementation in males, a gradual increase in CORT was observed during supplementation, peaking at DAY21. Passive coping strategies was preferred in the FST in RC (Regular Cage)- housed females exposed to FO while RC-housed CSO-fed males opted for an active climbing coping strategy. Increase locomotion and anxiolytic behaviour were observed in CSO-supplemented males (exposed to EE), while CSO by itself promoted social recognition in males. In contrast, sociability was improved in FO EE exposed females, indicating possible synergic effects. Adulthood hippocampal GR-ir expression was reduced at the hippocampal CA3 region in FO/RC and CSO/EE rat groups, which could have influenced memory consolidation and stress resilience. Overall, results from this study provided insights on positive effects associated with short-term adolescent n-3 PUFA supplementation in females, while male appeared to most benefited from soybean diet supplementation. Our fourth and last study assessed age- and sex-dependent influences of dietary supplementation on cognitive performance in the Barnes Maze Test. Our results showcase a gradual decrease in latencies to the escape box, as well as progressive decrease in working memory errors (WME) in adult compared to adolescent rats. Over the testing period, the FO females and CSO males showed improved performance through reduction of WMEs on specific days, which could subtend sex-related effects of dietary supplementations. However, while discrete effects of n-3 PUFA were more apparent in female rats, short-term supplementation appeared insufficient to promote consistent enhancement of visuospatial performance or cognitive flexibility that could be observed throughout the testing period. In conclusion, our findings support the importance of studying single and combined factors to understand overall impact. We were able to consistently demonstrate beneficial effects on coping strategies, stress reactivity, sociability, and cognitive performance of adolescence-targeted fish oil supplementation, especially in female rodents.

This thesis aims to uncover preliminary design relationships for an inlet of a split-wing electric distributed propulsion regional airliner. Several aspects of the inlet design were investigated, including: the overall thickness of the airfoil section with respect to the chord, inlet throat area, and lip radius. These parameters were investigated using several angles of attack and mass flow rates through the fan. Computational fluid dynamics, with a 2nd Order turbulence model was used and validated against World War II era data from NACA, as those studies were the most pertinent wind tunnel data available. Additionally, other works by Boeing, Empirical Systems Aerospace (ESAero), Rolling Hills Research, and the Air Force Research Laboratories (AFRL) were considered as part of this design tool tradespace. Future work considerations include utilizing an airfoil section designed for M = 0.6 or 0.65 cruise conditions as opposed to a symmetrical airfoil section, extruding the 2-D airfoil section discussed in this thesis for 3-D effects, and incorporating fan rotational physics into the simulations to better account for inlet Mach number effects.

Populations at risk for tuberculosis (TB) may have a low n-3 polyunsaturated fatty acid (PUFA) status. Our research previously showed that post-infection supplementation of n-3 long-chain PUFA (LCPUFA) in TB without TB medication was beneficial in n-3 PUFA sufficient but not in low-status C3HeB/FeJ mice. In this study, we investigated the effect of n-3 LCPUFA adjunct to TB medication in TB mice with a low compared to a sufficient n-3 PUFA status. Mice were conditioned on an n-3 PUFA-deficient (n- 3FAD) or n-3 PUFA-sufficient (n-3FAS) diet for 6 weeks before TB infection. Postinfection at 2 weeks, both groups were switched to an n-3 LCPUFA [eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA)] supplemented diet and euthanized at 4- and 14- days post-treatment. Iron and anemia status, bacterial loads, lung pathology, lung cytokines/chemokines, and lung lipid mediators were measured. Following 14 days of treatment, hemoglobin (Hb) was higher in the n-3FAD than the untreated n-3FAS group (p = 0.022), whereas the n-3FAS (drug) treated control and n-3FAS groups were not. Proinflammatory lung cytokines; interleukin-6 (IL-6) (p = 0.011), IL-1a (p = 0.039), MCP1 (p = 0.003), MIP1- a (p = 0.043), and RANTES (p = 0.034); were lower, and the antiinflammatory cytokine IL-4 (p=0.002) and growth factor GMCSF (p=0.007) were higher in the n-3FAD compared with the n-3FAS mice after 14 days. These results suggest that n-3 LCPUFA therapy in TB-infected mice, in combination with TB medication, may improve anemia of infection more in low n-3 fatty acid status than sufficient status mice. Furthermore, the low n-3 fatty acid status TB mice supplemented with n-3 LCPUFA showed comparatively lower cytokine-mediated inflammation despite presenting with lower pro-resolving lipid mediators.

No description available.

No / Human saphenous vein endothelial cells (HSVECs) derived from primary cultures of adult human veins constitute an excellent in vitro model for studying human endothelial metabolism. In this study we report the14C-labelled prostanoid profile of HSVECs under resting and stimulated conditions and the effect of the n-3 polyunsaturated fatty acids eicosapentaenoic acid and docosahexaenoic acid on them. Results indicate that HSVECs while under resting conditions produce mainly prostaglandin F2 ¿(PGF2 ¿). After stimulation with calcium ionophore A23187, the cells were found to synthesise PGI2, PGE2and PGF2¿as major products and thromboxane B2and PGD2as minor products. Production of14C-labelled hydroxyeicosatetraenoic acids was not detected. Eicosapentaenoic acid was found to inhibit basal and stimulated prostanoid production whereas docosahexaenoic acid inhibited basal but strongly increased stimulated prostanoid production. These results may offer the basis for further studies aiming to investigate targets for pharmacological intervention in inflammatory conditions.

La couche de nacre de la coquille de l'huître perlière Pinctada radiata des côtes tunisiennes est considérée comme un biomatériau ostéogénique prometteur. L’objectif de ce travail intitulé « Ostéogénie, intégration et qualité de la nacre d’un bivalve des côtes tunisiennes : Pinctada radiata (Leach, 1814) » consiste dans un premier temps à valoriser l’espèce P. radiata par sa qualité nutritionnelle par un suivi saisonnier de la composition de sa chair en lipides totaux et en phospholipides particulièrement les PC, PE, PS et PI. Les analyses effectuées ont montré que les lipides de P.radiata sont caractérisés par une richesse en acides gras polyinsaturés (AGPI) de la série n-3 qui dépasse 3 fois celle des AGPI de la série n-6. Ces AGPI de la série n-3 en particulier l’EPA (C20:5n-3) et le DHA (C22:6n-3), sont connus comme étant les AG les plus importants dans l’alimentation humaine puisqu’ils préviennent des maladies cardiovasculaires et des pathologies ostéo-articulaires. Par ailleurs, P. radiata de la région de Maharès présente la meilleure qualité de nacre en Tunisie. Les analyses biochimiques ont montré que cette région, constitue la meilleure localisation de cette espèce qui est loin des zones portuaires et des différentes origines de stress (pêche, exploitation, zone touristique etc…). En plus de cet aspect, la zone de Maharès renferme des pintadines présentant une bonne qualité en termes d’épaisseur de nacre. Nos résultats montrent que la composition, saisonnière, en acide gras des phospholipides et en particulier des glycérophospholipides (PE, PI, PS et PC) de la nacre est riche en acides gras saturés C14 :0, C16 :0 et C18 :0 particulièrement en hiver et dans un moindre degré au printemps. La nacre, substance ostéogénique, a été également caractérisée par un taux élevé de plusieurs AGPI de la série n-3 et n-6, particulièrement (18:3n-3, 18:4n-3, 20:5n-3, 22:5n-3, 22:6n-3 et le 20:4n-6). Pour démontrer les potentialités ostéogéniques des extraits de la nacre, nous avons utilisé un modèle "in vitro" utilisant 4 extraits lipidiques : l’extrait lipidique de la nacre de P.radiata (Ln), l’extrait lipidique de la chair de P.radiata (Lc), l’ESM (Ethanol soluble Matrix) de la nacre de P.radiata (Br) et l’ESM de la nacre de P.margaritifera (Bm). Nous avons comparé, in vitro, le pouvoir ostéogénique des extraits ESM des deux espèces P. radiata et P. margaritifera sur deux types de cellules les préchondrocytes ATDC5 et les préostéoblastes murins MC3T3. Les différents extraits (Ln, Lc, Br et Bm) induisent l’engagement des cellules MC3T3 vers le lignage ostéoblastique par l’activation des promoteurs des gènes spécifiques du tissu osseux, tels que: le collagène de type 1, l’ostéocalcine (OC), l’ostéopontine(OP) et le Runx2. Ces extraits induisent aussi l’engagement des cellules ATDC5 vers la différenciation endochondrale par l’activation des promoteurs des gènes spécifiques du tissu osseux, tels que: le collagène de type 1 alpha-1 (Col1a1), l’Aggrécane et le collagène de type X alpha-1 (ColXA1). De plus, nous remarquons que la fraction organique ou ESMr(Br) en comparaison avec celle de P.margaritifera (Bm) présente également les propriétés stimulantes de la nacre et la stimulation est même beaucoup plus importante. Ces résultats mettent en évidence, dans les modèles expérimentaux mis en oeuvre, l’intérêt des lipides. Ces derniers semblent jouer un rôle important dans cette stimulation. De plus, nous pouvons penser à la possibilité de l’association des molécules de nacre ou de biominéralisation avec les acides gras de la nacre et de la chair dans les défauts osseux à travers les sites actifs de l’os ou du cartilage humain présentant les différentes pathologies ostéarticulaires / The nacre layer of the shell of the pearl oyster Pinctada radiata of tunisian coast is considered a promising osteogenic biomaterial. The objective of this work entitled "Osteogenie, integration and quality of nacre of a tunisian coast bivalve: Pinctada radiata (Leach, 1814)" is a first step to enhance the species P.radiata its nutritional quality by seasonal monitoring of the composition of the flesh of total lipids and phospholipids in particular PC, PE, PS and PI. The analyzes showed that lipids of P.radiata are characterized by rich in polyunsaturated fatty acids (PUFAs) of the n-3 more than 3 times that of PUFAs n-6 series. These PUFAs of the n-3 series particularly EPA (C20: 5n-3) and DHA (C22: 6n-3) are known to be the most important AG in the food as prevent of the cardiovascular disease, and joint/ bone pathologies. Moreover, P. radiata of Mahares region has the best quality of nacre in Tunisia. Biochemical analyzes showed that this region is the best location of this species that is far from the port areas and different sources of stress (fishing, exploitation, tourist area etc ...). In addition to this aspect, the area contains pintadines having good quality in terms of thickness of nacre. Our results show that the seasonal composition of fatty acid of phospholipids in particular glycerophospholipids (PE, PI, PS and PC) nacre is rich in saturated fatty acids C14: 0, C16: 0 and C18: 0 especially in winter and spring in a lesser degree. Nacre, osteogenic substance, was also characterized by a high rate of PUFA of the n-3 and n-6 rate, especially (18: 3n-3, 18: 4n-3, 20: 5n-3, 22 5n-3, 22: 6n-3 and 20: 4n-6). To demonstrate the osteogenic potential of extracts of nacre, we have established an "in vitro" model using 4 lipid extracts: the lipid extract of nacre P.radiata (Ln); the lipid extract of the flesh of P.radiata (Lc), ESM (Ethanol soluble Matrix) of the mother-of P.radiata (Br) and ESM nacre of P. margaritifera (Bm). We compared “in vitro” osteogenic power ESM extracts of both species P. radiata and P. margaritifera on two types of cells the préchondrocytes ATDC5 and the murine preosteoblasts MC3T3. The different extracts (Ln, Lc, Br and Bm) induce engagement MC3T3 osteoblast lineage cells to the activation of the promoters of specific genes of bone tissue, such as collagen type 1, osteocalcin (OC), osteopontin (OP) and Runx2. These extracts also induce the commitment of ATDC5 cells to endochondral differentiation by activating specific genes promoters of bone tissue, such as collagen type 1 alpha 1 (COL1A1), the aggrecan and collagen type alpha 1-X (ColXA1). Moreover, we note that the organic fraction or ESMR (Br) compared with that of P. margaritifera (Bm) also has stimulant properties of nacre and the stimulation is even more important. These results demonstrate, in experimental models used, the interest of lipids. They seem to play an important role in this stimulation. Moreover, we can think about the possibility of the association of molecules or nacre biomineralization with the fatty acids of the nacre and flesh in bone defects through the active sites of bone or cartilage presenting the human osteoarticular different pathologies