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Impact de différents régimes durant la lactation sur le développement de pathologies cardio-métaboliques chez des souris RCIU

Abstract : Intra-Uterine Growth Retardation (IUGR) is associated with increased risk of cardio-metabolic diseases. Furthermore, previous studies also indicated that changing nutrition during the early post-natal period could worsen pathologies later on. In order to study mechanisms involved in programming of these pathologies, our laboratory developed a mouse model of IUGR- induced by feeding pregnant mice with an isocaloric/ low-protein diet - and whose nutrition during lactation was modulated by normalizing litter sizes to induce overfeeding, normal feeding or restriction. Restriction during lactation can protect IUGR mice from the development of cardio-metabolic pathologies even in aged mice. In contrast, both normal feeding or overfeeding during lactation exacerbate weight gain by 1 month of age onward, and induce an insulin resistance, a steatosis and an arterial hypertension with age. Molecular alterations of AKT phosphorylation in liver of mice were observed before the appearance of insulin resistance. Interestingly, this could be promoted by the permanent decrease in AKT protein levels that is associated with a decrease in the positive H3K4me3 histone mark in Akt promoter. Furthermore, an alteration in H3K4me3 levels was also observed in the promoter of microRNA17-92a cluster gene. miR-19a, a member of this cluster, is known to regulate PTEN translation, an AKT inhibitor. In agreement, post-transcriptional regulation of PTEN seems to be altered in adult IUGR-N and IUGR-O male mice. Currently, importance of this microRNA is studied in a human cohort.
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Sarah Saget. Impact de différents régimes durant la lactation sur le développement de pathologies cardio-métaboliques chez des souris RCIU. Physiologie [q-bio.TO]. Sorbonne Université, 2018. Français. ⟨NNT : 2018SORUS118⟩. ⟨tel-02949752⟩

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