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Pourquoi la thérapie HAART remanie-t-elle les différents sites du tissu adipeux de manière hétérogène ? : importance de l’origine des dépôts, modélisation et mécanismes moléculaires

Abstract : The adipose tissue (AT) is distributed throughout the body in different depots. There are two distinct types with specific functions: the white adipose tissue is used as an energetic reservoir and stores the lipids whereas the brown adipose tissue allows the thermogenesis. By its functionalities and its endocrinal capacity, the AT ensures the energetic homeostasis maintenance. Severe metabolic disorders result from an excess found during obesity or a remodelling in the lipodystrophies. Some of them have a genetic origin, the others are induced by drugs such as the HIV-protease inhibitors (PI) administered in the antiretroviral therapy against HIV. The adipose progenitor (AP) pool present in each depot is necessary for the maintenance of this tissue because it allows to renew the adipocyte stock. We characterized and identified new genes involved in the autocrine/paracrine Activin A loop which is responsible for AP pool self-renewal of whom is IER3. Its expression increases in obese patients and decreases under PI treatment. The modelling of the different depots shows that PI inhibit preferentially PA self-renewal or adipose differentiation depending on their localisation. Thus, lipodystrophies induced by antiretroviral therapy would have multifactorial causes. Finally, our results reveal PI dramatically and selectively reduce the brown adipocyte production. These effects should be considered in the context of inappropriate brown adipose tissue development in order to correct metabolic disorders associated to some pathologies.
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https://tel.archives-ouvertes.fr/tel-01827020
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Submitted on : Tuesday, September 11, 2018 - 10:44:17 AM
Last modification on : Wednesday, October 14, 2020 - 4:23:35 AM
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  • HAL Id : tel-01827020, version 2

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Christophe Ravaud. Pourquoi la thérapie HAART remanie-t-elle les différents sites du tissu adipeux de manière hétérogène ? : importance de l’origine des dépôts, modélisation et mécanismes moléculaires. Sciences agricoles. Université Côte d'Azur, 2017. Français. ⟨NNT : 2017AZUR4016⟩. ⟨tel-01827020v2⟩

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