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Caractérisation et fonction des vésicules extracellulaires sur le métabolisme adipocytaire : rôle du morphogène Sonic Hedgehog

Abstract : Extracellular vesicles (EV), including microparticles (MP) and exosomes, are able to modulate target cell function through exchange or transfer of biological material. Although EV are present in the blood of healthy individuals, an elevated quantity of circulating EV is associated with cardiovascular diseases, which obesity is a major cardiovascular risk factor. Nevertheless, few studies have reported the ability of adipocytes to release EV and their implication in adipose tissue metabolism. First of all, we could determine morphological and biochemical features of adipocyte-derived exosomes and MP through a combination of methods. We were able to demonstrate an increase in adipocyte EV production in a murine model of obesity. Proteomic analysis of adipocyte EV further revealed a specific enrichment of proteins crucial for glucose and lipid metabolism and related to inflammation in MP and exosomes respectively. We then evaluated the ability of lymphocytes-derived MP harboring the Sonic Hedgehog morphogen to control adipocyte differentiation. Activation of the Hedgehog canonical pathway inhibited adipogenesis, as did MPHh+. Surprisingly, although Smo dependent, inhibitory potential of such MP did not involve the Gli transcription factors. We show that MPHh+ inhibit adipocyte differentiation through a Smo/Lkb1/Ampk axis as does a new agonist of Smo, GSA-10. Our results demonstrate, on one hand, the ability of adipocyte to release EV and on the other hand, the capacity of MPHh+ to control adipogenesis through a non-canonical Hh signaling pathway. In conclusion, EV might contribute to obesity related metabolic dysfunctions through systemic regulation of metabolic pathways.
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  • HAL Id : tel-02387036, version 1

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Audrey Fleury. Caractérisation et fonction des vésicules extracellulaires sur le métabolisme adipocytaire : rôle du morphogène Sonic Hedgehog. Médecine humaine et pathologie. Université d'Angers, 2015. Français. ⟨NNT : 2015ANGE0079⟩. ⟨tel-02387036⟩

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