Arsenic induces metabolome remodeling in mature human adipocytes.

Détails

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Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_513BAB55CAFC
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Arsenic induces metabolome remodeling in mature human adipocytes.
Périodique
Toxicology
Auteur⸱e⸱s
Gasser M., Lenglet S., Bararpour N., Sajic T., Vaucher J., Wiskott K., Augsburger M., Fracasso T., Gilardi F., Thomas A.
ISSN
1879-3185 (Electronic)
ISSN-L
0300-483X
Statut éditorial
Publié
Date de publication
12/2023
Peer-reviewed
Oui
Volume
500
Pages
153672
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
Human lifetime exposure to arsenic through drinking water, food supply or industrial pollution leads to its accumulation in many organs such as liver, kidneys, lungs or pancreas but also adipose tissue. Recently, population-based studies revealed the association between arsenic exposure and the development of metabolic diseases such as obesity and type 2 diabetes. To shed light on the molecular bases of such association, we determined the concentration that inhibited 17% of cell viability and investigated the effects of arsenic acute exposure on adipose-derived human mesenchymal stem cells differentiated in vitro into mature adipocytes and treated with sodium arsenite (NaAsO <sub>2</sub> , 10 nM to 10 µM). Untargeted metabolomics and gene expression analyses revealed a strong dose-dependent inhibition of lipogenesis and lipolysis induction, reducing the cellular ability to store lipids. These dysregulations were emphasized by the inhibition of the cellular response to insulin, as shown by the perturbation of several genes and metabolites involved in the mentioned biological pathways. Our study highlighted the activation of an adaptive oxidative stress response with the strong induction of metallothioneins and increased glutathione levels in response to arsenic accumulation that could exacerbate the decreased insulin sensitivity of the adipocytes. Arsenic exposure strongly affected the expression of arsenic transporters, responsible for arsenic influx and efflux, and induced a pro-inflammatory state in adipocytes by enhancing the expression of the inflammatory interleukin 6 (IL6). Collectively, our data showed that an acute exposure to low levels of arsenic concentrations alters key adipocyte functions, highlighting its contribution to the development of insulin resistance and the pathogenesis of metabolic disorders.
Mots-clé
Humans, Arsenic/metabolism, Diabetes Mellitus, Type 2, Adipose Tissue/metabolism, Adipocytes, Insulin/metabolism, Insulin Resistance, Metabolome, Arsenic, Human adipocytes, Lipid metabolism, Metabolomics, Oxidative stress response
Pubmed
Web of science
Open Access
Oui
Financement(s)
Fonds national suisse
Création de la notice
14/11/2023 16:29
Dernière modification de la notice
10/01/2024 8:15
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