Conséquences Moléculaires de l'Exposition du Tissu Adipeux Humain à des Xénobiotiques Environnementaux

Abstract : Adipose tissue is a major regulator of energetic homeostasis in organisms. This tissue is filled with lipids, representing a major storage organ for many lipophilic environmental contaminants. The consequences of this accumulation, and more generally of the exposure of human adipose tissue to such pollutants have been poorly investigated. However, by modulating the physiological functions or the development of this tissue, environmental chemicals could play a role in the development of diseases like obesity or diabetes. The aim of this thesis was to improve our knowledge on the consequences of the exposure of human adipose tissue to environmental xenobiotics. First, we investigated the in situ metabolic capacities toward xenobiotics in human adipose tissue, by characterizing the expression of the 23 isoformes of cytochromes P450 involved in xenobiotic metabolism. Our results showed that only CYP1B1 and CYP2U1 were expressed in this tissue, and that the AhR induction pathway was functional, whereas CAR and PXR induction pathways were not. Then, we used an untargeted, "top-down", transcriptomic and 1H-NMR based approach, to characterize the perturbations induced by the treatment of primary cultures of in vitro differentiated human preadipocytes with 2 pollutants: 2,3,7,8-tetrachlorodibenzo-p-dioxine (TCDD) and mono-2-ethyl hexyl-phthalate (MEHP). Data integration allowed the generation of many hypothesis regarding the mechanisms of toxicity induced by both compounds. MEHP in particular seemed to possess a pro-differentiating effect on human preadipocytes and to induce neoglycerogenesis in human adipocytes, two mechanisms through which this compound could have an obesogenic effect in human.
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Toxicology. AgroParisTech, 2010. French. <NNT : 2010AGPT0039>


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Sandrine Ellero. Conséquences Moléculaires de l'Exposition du Tissu Adipeux Humain à des Xénobiotiques Environnementaux. Toxicology. AgroParisTech, 2010. French. <NNT : 2010AGPT0039>. <pastel-00610847>

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