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Caractérisation des effets métaboliques d’un mélange de polluants à faibles doses dans un modèle de souris déficientes en oestrogènes

Abstract : Menopause is a risk factor associated with the development of metabolic diseases. Because of estrogen deficiency, postmenopausal women may be at particular risk when exposed to chemical agents that can disrupt the endocrine system. To get more insight, we have developed a model of ovariectomized mice supplemented or not with estradiol (E2), and chronically exposed to a mixture of pollutants (TCDD, PCB153, DEHP and BPA) added to an obesogenic diet. Each pollutant was used at a dose close to the Tolerable Daily Intake dose, and the exposure had covered different stages of development, including or not the maternal period (gestation + lactation). Our results indicate that in diet-induced obesity, ovariectomy triggered weight gain, increase glucose intolerance and insulin resistance. This phenotype was associated with decreased estrogenic signaling in liver and deregulation of adipogenesis and inflammation in adipose tissues. Interestingly, the mixture of pollutants reduced the deleterious impact of ovariectomy on the metabolic phenotype, possibly through an alleviation of estrogenic signaling in both liver and adipose tissues. These data were not reproduced in mice not exposed to pollutants during the maternal life. In conclusion, the mixture of pollutants displayed some estrogeno-mimetic activity. This could have implications in understanding the role of environmental pollutants in the development of metabolic diseases in women in menopausal transition.
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https://tel.archives-ouvertes.fr/tel-02569438
Contributor : Abes Star :  Contact
Submitted on : Monday, May 11, 2020 - 12:39:59 PM
Last modification on : Monday, October 19, 2020 - 10:58:30 AM

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  • HAL Id : tel-02569438, version 1

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Benoit Julien. Caractérisation des effets métaboliques d’un mélange de polluants à faibles doses dans un modèle de souris déficientes en oestrogènes. Endocrinologie et métabolisme. Université de Lyon, 2019. Français. ⟨NNT : 2019LYSE1092⟩. ⟨tel-02569438⟩

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