Assessment of endocrine disruptor impacts on lipid metabolism in a fatty acid-supplemented HepaRG human hepatic cell line.

Autor: Bernal K; Université Paris Cité, T3S, Inserm UMR-S 1124, 45 Rue des Saints Pères, Paris, France., Touma C; Inserm, EHESP, Irset (Institut de Recherche en Santé Environnement et Travail) - UMR-S 1085, Université de Rennes, France., Le-Grand B; Université Paris Cité, T3S, Inserm UMR-S 1124, 45 Rue des Saints Pères, Paris, France., Rose S; Inserm, EHESP, Irset (Institut de Recherche en Santé Environnement et Travail) - UMR-S 1085, Université de Rennes, France., Degerli S; Université Paris Cité, T3S, Inserm UMR-S 1124, 45 Rue des Saints Pères, Paris, France., Genêt V; Inserm, EHESP, Irset (Institut de Recherche en Santé Environnement et Travail) - UMR-S 1085, Université de Rennes, France., Lagadic-Gossmann D; Inserm, EHESP, Irset (Institut de Recherche en Santé Environnement et Travail) - UMR-S 1085, Université de Rennes, France., Coumoul X; Université Paris Cité, T3S, Inserm UMR-S 1124, 45 Rue des Saints Pères, Paris, France., Martin-Chouly C; Inserm, EHESP, Irset (Institut de Recherche en Santé Environnement et Travail) - UMR-S 1085, Université de Rennes, France., Langouët S; Inserm, EHESP, Irset (Institut de Recherche en Santé Environnement et Travail) - UMR-S 1085, Université de Rennes, France., Blanc EB; Université Paris Cité, T3S, Inserm UMR-S 1124, 45 Rue des Saints Pères, Paris, France. Electronic address: etienne.blanc@u-paris.fr.
Jazyk: angličtina
Zdroj: Chemosphere [Chemosphere] 2024 Feb; Vol. 349, pp. 140883. Date of Electronic Publication: 2023 Dec 11.
DOI: 10.1016/j.chemosphere.2023.140883
Abstrakt: The incidence of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing worldwide. This disease encompasses several stages, from steatosis to steatohepatitis and, eventually, to fibrosis and cirrhosis. Exposure to environmental contaminants is one of the risk factors and an increasing amount of evidence points to a role for endocrine disrupting compounds (EDCs). This study assesses the impact of selected EDCs on the formation of lipid droplets, the marker for steatosis in a hepatic model. The mechanisms underlying this effect are then explored. Ten compounds were selected according to their obesogenic properties: bisphenol A, F and S, butyl-paraben, cadmium chloride, p,p'-DDE, DBP, DEHP, PFOA and PFOS. Using a 2D or 3D model, HepaRG cells were exposed to the compounds with or without fatty acid supplementation. Then, the formation of lipid droplets was quantified by an automated fluorescence-based method. The expression of genes and proteins involved in lipid metabolism and the impact on cellular respiration was analyzed. The formation of lipid droplets, which is revealed or enhanced by oleic acid supplementation, was most effectively induced by p,p'-DDE and DEHP. Experiments employing either 2D or 3D culture conditions gave similar results. Both compounds induced the expression of PLIN2. p,p'-DDE also appears to act by decreasing in fatty acid oxidation. Some EDCs were able to induce the formation of lipid droplets, in HepaRG cells, an effect which was increased after supplementation of the cells with oleic acid. A full understanding of the mechanisms of these effects will require further investigation. The novel automated detection method described here may also be useful in the future as a regulatory test for EDC risk assessment.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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