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T. Résumé-de,

, Durant ma thèse, j'ai étudié l'effet de différentes nutritions appliquées de manière transitoire durant la lactation dans l'induction de pathologies cardio-métaboliques adultes sur un modèle murin de RCIU et je me suis intéressée plus particulièrement aux mécanismes épigénétiques pouvant être impliqués dans l'apparition d'une résistance à l'insuline. Pour cela, le laboratoire a développé un modèle de souris nées avec un RCIU induit par un régime hypo-protéique/iso-calorique de la mère durant sa dernière semaine de gestation. A la naissance, les portées ont été normalisées à 3, 6 ou 10 souriceaux par mère afin d'induire respectivement une surnutrition, une nutrition normale ou une restriction alimentaire durant la lactation. J'ai tout d'abord pu montrer que ce modèle reproduit chez les souris mâles de nombreux troubles métaboliques rencontrés chez l'Humain. En effet, la restriction durant la lactation des souriceaux RCIU les protège de l'apparition des pathologies cardiométaboliques même à un âge avancé. A l'inverse, la nutrition normale (RCIU-N) ou la surnutrition (RCIU-S) durant la lactation des souriceaux RCIU induit un surpoids dès l'âge de 1 mois, puis une résistance à l'insuline, une accumulation de lipides au niveau hépatique et une hypertension artérielle avec l'âge. La résistance à l'insuline est associée à une altération de la phosphorylation d'AKT. Celle-ci pourrait être favorisée par la diminution permanente des taux d'AKT. Cette baisse est associée à une dérégulation épigénétique au niveau des histones, observée via un ChIPSeq (NGS) contre la marque associée à la régulation de la transcription, H3K4me3. D'autre part, mes résultats mettent aussi en évidence une augmentation cohérente de l, Le Retard de Croissance Intra-Utérin (RCIU) concerne environ 5% des naissances dans les pays développés et est associé à un risque accru de développer des pathologies cardiométaboliques à long terme. En accord avec le concept de l'origine développementale de la santé et des pathologies adultes (DOHaD)

, L'importance de ce miARN est en cours d'étude dans une cohorte humaine. L'ensemble de ces données renforcent l'importance d'une nutrition adéquate pendant la période post-natale précoce pour les petits nés avec un RCIU afin d'éviter l'émergence de pathologies à l'âge adulte et ouvre la possibilité de disposer dans le futur d'un potentiel bio-marqueur prédictif d'une altération métabolique