Omega-3 Fatty Acids from Fish Oil Lower Anxiety, Improve Cognitive Functions and Reduce Spontaneous Locomotor Activity in a Non-Human Primate

Omega-3 (ω3) polyunsaturated fatty acids (PUFA) are major components of brain cells membranes. ω3 PUFA-deficient rodents exhibit severe cognitive impairments (learning, memory) that have been linked to alteration of brain glucose utilization or to changes in neurotransmission processes. ω3 PUFA supplementation has been shown to lower anxiety and to improve several cognitive parameters in rodents, while very few data are available in primates. In humans, little is known about the association between anxiety and ω3 fatty acids supplementation and data are divergent about their impact on cognitive functions. Therefore, the development of nutritional studies in non-human primates is needed to disclose whether a long-term supplementation with long-chain ω3 PUFA has an impact on behavioural and cognitive parameters, differently or not from rodents. We address the hypothesis that ω3 PUFA supplementation could lower anxiety and improve cognitive performances of the Grey Mouse Lemur (Microcebus murinus), a nocturnal Malagasy prosimian primate. Adult male mouse lemurs were fed for 5 months on a control diet or on a diet supplemented with long-chain ω3 PUFA (n = 6 per group). Behavioural, cognitive and motor performances were measured using an open field test to evaluate anxiety, a circular platform test to evaluate reference spatial memory, a spontaneous locomotor activity monitoring and a sensory-motor test. ω3-supplemented animals exhibited lower anxiety level compared to control animals, what was accompanied by better performances in a reference spatial memory task (80% of successful trials vs 35% in controls, p<0.05), while the spontaneous locomotor activity was reduced by 31% in ω3-supplemented animals (p<0.001), a parameter that can be linked with lowered anxiety. The long-term dietary ω3 PUFA supplementation positively impacts on anxiety and cognitive performances in the adult mouse lemur. The supplementation of human food with ω3 fatty acids may represent a valuable dietary strategy to improve behavioural and cognitive functions

Sex-specific epigenetic impact of preconceptional maternal weight loss on foeto-placental development

National audienc

Maternal preconceptional weight loss: impact on fetoplacental development and on epigenetic machinery genes expression

International audienc

Effects of preconceptional maternal weight trajectories on offspring health

Since the 90’s, obesity became pandemic. Nutritional environment has an important impact during development, leading to the later onset of non-communicable diseases. Maternal environment may affect offspring development through epigenetic mechanisms, regulating gene expression and microbiota, which is a major actor of metabolism. In order to reduce fertility troubles and obstetrical complications caused by obesity, it is now recommended for women who plan a pregnancy to lose weight before conception. However, the long-term effects of this preconception weight loss are not well described in the literature. We aim to identify whether maternal weight loss prior to conception can prevent the development of metabolic syndrome at the adult age. We previously highlighted in a mouse model the high sensitivity of the epigenetic machinery gene expression, and particularly histone acetylation pathway, to maternal obesity. Preconceptional weight loss appears beneficial for fetal growth, but some effects of previous obesity were retained in offspring transcriptome. During my PhD, I will precise:- the offspring phenotype using metabolomics of adult liver, olfactory bulb and hypothalamus (LC-HRMS),- the epigenomic analysis by an histone acetylation study in fetal liver (ChIP-seq,- the microbiota component with an analysis of maternal and offspring gut microbiota (16S rRNA-seq).The correlation of metabolic parameters, epigenomic state and gut microbiota will give us information about the mechanisms of maternal diet’s effects and their participation to adult health conditioning

Epigenetics and Nutrition:maternal nutrition impacts on placental development and health of offspring

L’environnement au cours du développement précoce de l’individu conditionne le phénotype à long terme, en particulier la susceptibilité, ou non, à développer des maladies non transmissibles. Cette notion des Origines Développementales de la Santé et des Maladies (DOHaD pour Developmental Origins of Health and Disease) s’appuie sur de nombreuses études épidémiologiques ainsi que sur des modèles animaux. Ainsi la nutrition riche et l’obésité parentale peuvent prédisposer l’enfant à développer lui-même des pathologies métaboliques et cardiovasculaires à l’âge adulte. Les mécanismes sous-jacents incluent une dysfonction placentaire qui va impacter la croissance et le développement du fœtus. Les mécanismes épigénétiques, qui modulent l’expression des gènes et permettent d’établir une identité cellulaire, sont sensibles à des facteurs de l’environnement, tels que la nutrition et le métabolisme énergétique. Les marques épigénétiques peuvent donc permettre la mémorisation de l’environnement précoce et induire à long terme une altération de la fonction des organes, conditionnant ainsi la susceptibilité à la pathologie. Nous avons montré que le placenta est sensible à l’alimentation et au statut métabolique maternels d’un point de vue histologique, transcriptionnel et épigénétique. Par ailleurs, un dimorphisme sexuel est très marqué dans la réponse placentaire à l’environnement maternel. Des mécanismes épigénétiques pourraient être à la base de cette réactivité différentielle entre femelle et mâle. La notion de DOHaD ne peut plus être ignorée en Biologie de la Reproduction aujourd’hui. La prévention doit tenir compte de ce nouveau paradigme. La recherche est encore nécessaire pour bien comprendre les mécanismes de ce conditionnement précoce et le dimorphisme sexuel marqué de ce phénotype

Obésité et perte de poids maternelles : programmation épigénétique dans le placenta et effets sur le phénotype des descendants adultes

International audienc

(n-3) Polyunsaturated Fatty Acid Deficiency Reduces the Expression of Both Isoforms of the Brain Glucose Transporter GLUT1 in rats

International audienc

Omega 3 fatty acids and energy supply: impact on glucose transport

National audienc

Le statut métabolique maternal préconceptionnel influence le métabolisme hépatique des descendants mâles

National audienc