Rôle des déséquilibres nutritionnels pendant la période fœtale et postnatale précoce dans le développement à l'âge adulte de l'athérosclérose // Role of nutritional disequilibrium during the fetal and early postnatal period on the development of atheroscl

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The prevalence of obesity and metabolic disorders reaches the level of global pandemic and is associated with cardiovascular diseases, which is a major cause of morbidity and mortality. Among metabolic disorders, altered circulating concentrations of lipids and lipoproteins are major components of the development of cardiometabolic diseases (CMD). This is notably the case for atherosclerosis which may lead to heart failure.

The current context of obesity and dyslipidemia is particularly worrying for women of childbearing age who are nowadays more frequently exposed to malnutrition, and especially to diets rich in saturated fatty acids, sugar and cholesterol. Indeed, in addition to impact health of the future mum, these diets may also impact the progeny. In agreement with the Developmental Origin of Heath and adult Diseases (DOHaD) hypothesis, early nutritional disequilibrium is strongly associated with the appearance of diseases in adulthood, notably the cardiometabolic ones. In addition to association observed with development of obesity or diabetes, some evidences from both familial hypercholesterolemia's cohorts and preclinical models suggest that fetuses and neonates exposed to diets rich in fat and cholesterol through their mother may be more at risk to develop atherosclerosis latter on. However, mechanisms involved are not fully understood.

Taking advantage of a dedicated preclinical mouse model with humanized lipoprotein profile, objectives of this thesis are to decipher the complex interactions between diet in future mums, regulation of the lipid metabolism, and atherosclerosis development in the progeny. In addition, since some lipid species have been associated with anti-inflammatory and cardioprotective bioactivities, the opportunity to prevent atherosclerosis development with specific nutritional complements will be evaluated. This project will involve integrated physiological (ITT, GTT), histological (IHC), biochemical (ELISA, WB) and molecular approaches (RT-qPCR) in mice. A particular attention will be paid to epigenetic modifications (meDNA, miR, Histone PTM) that could be involved. This project may offer opportunities to unveil potential new therapeutic targets and circulating biomarkers to highlight people at risk to develop atherosclerosis.
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Début de la thèse : 01/10/2025

Contrat doctoral

Concours pour un contrat doctoral

Sorbonne Université SIM (Sciences, Ingénierie, Médecine)

394 Physiologie, physiopathologie et thérapeutique

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