Combinatorial pathway disruption is a powerful approach to delineate metabolic impacts of endocrine disruptors

Kévin Bernal (1) , Charbel Touma (2) , Chedi Erradhouani (3) , Talía Boronat-Belda (4, 5) , Lucas Gaillard (1) , Sara Al Kassir (6) , Hélène Le Mentec (2) , Corinne Martin-Chouly (2) , Normand Podechard (2) , Dominique Lagadic-Gossmann (2) , Sophie Langouet (2) , François Brion (3) , Anja Knoll-Gellida (6) , Patrick Babin (6) , Iva Sovadinova (7) , Pavel Babica (7) , Karine Andreau (1) , Robert Barouki (1) , Jan Vondracek (8) , Paloma Alonso-Magdalena (4, 5) , Etienne Blanc (1) , Min Ji Kim (1) , Xavier Coumoul (1)

1 T3S - UMR_S 1124 - Toxicité environnementale, cibles thérapeutiques, signalisation cellulaire
2 Irset - Institut de recherche en santé, environnement et travail
3 INERIS - Institut National de l'Environnement Industriel et des Risques
4 CIBERDEM - Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas
5 IDIBELL - Institut d'Investigació Biomèdica de Bellvitge [Barcelone]
6 U1211 INSERM/MRGM - Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux)
7 MUNI - Masaryk University [Brno]
8 IBP / CAS - Institute of Biophysics of the Czech Academy of Sciences

The prevalence of metabolic diseases, such as obesity, diabetes, metabolic syndrome and chronic liver diseases among others, has been rising for several years. Epidemiology and mechanistic (in vivo, in vitro and in silico) toxicology have recently provided compelling evidence implicating the chemical environment in the pathogenesis of these diseases. In this review, we will describe the biological processes that contribute to the development of metabolic diseases targeted by metabolic disruptors, and will propose an integrated pathophysiological vision of their effects on several organs. With regard to these pathomechanisms, we will discuss the needs, and the stakes of evolving the testing and assessment of endocrine disruptors to improve the prevention and management of metabolic diseases that have become a global epidemic since the end of last century.

Keywords: TBT; appetite; bisphenol; dioxin; inflammation; insulin resistance; microbiota; perfluorinated compounds; phthalate

Domains: Life Sciences [q-bio]

Kévin Bernal, Charbel Touma, Chedi Erradhouani, Talía Boronat-Belda, Lucas Gaillard, et al.. Combinatorial pathway disruption is a powerful approach to delineate metabolic impacts of endocrine disruptors. FEBS Letters, 2022, ⟨10.1002/1873-3468.14465⟩. ⟨hal-03788441⟩