Titre
PPAR disruption: Cellular mechanisms and physiological consequences
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Rotman, N.
Auteure/Auteur
Haftek-Terreau, Z.
Auteure/Auteur
Luecke, S.
Auteure/Auteur
Feige, J.
Auteure/Auteur
Gelman, L.
Auteure/Auteur
Desvergne, B.
Auteure/Auteur
Wahli, W.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
0009-4293
Statut éditorial
Publié
Date de publication
2008
Volume
62
Numéro
5
Première page
340
Dernière page/numéro d’article
344
Peer-reviewed
Oui
Langue
anglais
Résumé
Endocrine disruption is defined as the perturbation of the endocrine system, which includes disruption of nuclear hormone receptor signalling. Peroxisome proliferator-activated receptors (PPARs) represent a family of nuclear receptors that has not yet been carefully studied with regards to endocrine disruption, despite the fact that PPARs are known to be important targets for xenobiotics. Here we report a first comprehensive approach aimed at defining the mechanistic basis of PPAR disruption focusing on one chemical, the plasticizer monethylhexyl phthalate (MEHP), but using a variety of methodologies and models. We used mammalian cells and a combination of biochemical and live cell imaging techniques to show that MEHP binds to PPAR gamma and selectively regulates interactions with coregulators. Micro-array experiments further showed that this selectivity is translated at the physiological level during adipocyte differentiation. In that context, MEHP functions as a selective PPAR modulator regulating only a subset of PPAR gamma target genes compared to the action of a full agonist. We also explored the action of MEHP on PPARs in an aquatic species, Xenopus laevis, as many xenobiotics are found in aquatic ecosystems. In adult males, micro-array data indicated that MEHP influences liver physiology, possibly through a cross-talk between PPARs and estrogen receptors (ER). In early Xenopus laevis embryos, we showed that PPAR beta/delta exogenous activation by an agonist or by MEHP affects development. Taken together our results widen the concept of endocrine disruption by pinpointing PPARs as key factors in that process.
PID Serval
serval:BIB_E09B96427B2B
Date de création
2009-04-06T14:56:50.124Z
Date de création dans IRIS
2025-05-21T07:08:24Z