Cadmium acute exposure induces metabolic and transcriptomic perturbations in human mature adipocytes.

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State: Public
Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_39F3DD933D67
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Cadmium acute exposure induces metabolic and transcriptomic perturbations in human mature adipocytes.
Journal
Toxicology
Author(s)
Gasser M., Lenglet S., Bararpour N., Sajic T., Wiskott K., Augsburger M., Fracasso T., Gilardi F., Thomas A.
ISSN
1879-3185 (Electronic)
ISSN-L
0300-483X
Publication state
Published
Issued date
30/03/2022
Peer-reviewed
Oui
Volume
470
Pages
153153
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Obesity is considered as a major public health concern with strong economic and social burdens. Exposure to pollutants such as heavy metals can contribute to the development of obesity and its associated metabolic disorders, including type 2 diabetes and cardiovascular diseases. Adipose tissue is an endocrine and paracrine organ that plays a key role in the development of these diseases and is one of the main target of heavy metal accumulation. In this study, we determined by inductively coupled plasma mass spectrometry cadmium concentrations in human subcutaneous and visceral adipose tissues, ranging between 2.5 nM and 2.5 µM. We found a positive correlation between cadmium levels and age, sex and smoking status and a negative correlation between cadmium and body mass index. Based on cadmium adipose tissue concentrations found in humans, we investigated the effects of cadmium exposure, at concentrations between 1 nM and 10 µM, on adipose-derived human mesenchymal stem cells differentiated into mature adipocytes in vitro. Transcriptomic analysis highlighted that such exposure altered the expression of genes involved in trace element homeostasis and heavy metal detoxification, such as Solute Carrier Family transporters and metallothioneins. This effect correlated with zinc level alteration in cells and cellular media. Interestingly, dysregulation of zinc homeostasis and transporters has been particularly associated with the development of obesity and type 2 diabetes. Moreover, we found that cadmium exposure induces the pro-inflammatory state of the adipocytes by enhancing the expression of genes such as IL-6, IL-1B and CCL2, cytokines also induced in obesity. Finally, cadmium modulates various adipocyte functions such as the insulin response signaling pathway and lipid homeostasis. Collectively, our data identified some of the cellular mechanisms by which cadmium alters adipocyte functions, thus highlighting new facets of its potential contribution to the progression of metabolic disorders.
Keywords
Adipocytes/metabolism, Adipose Tissue/metabolism, Cadmium/toxicity, Diabetes Mellitus, Type 2/genetics, Humans, Insulin/metabolism, Metabolic Diseases, Obesity/chemically induced, Obesity/genetics, Transcriptome, Zinc/metabolism, Adipose tissue concentrations, Cadmium, Cellular homeostasis, Human adipocytes, Metallothioneins, SLC transporters
Pubmed
Web of science
Open Access
Yes
Create date
21/03/2022 10:26
Last modification date
17/05/2022 6:36
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