| Title |
Integrated transcriptomics and metabolomics reveal signatures of lipid metabolism dysregulation in HepaRG liver cells exposed to PCB 126
|
|---|---|
| Published in |
Archives of Toxicology, June 2018
|
| DOI | 10.1007/s00204-018-2235-7 |
| Pubmed ID | |
| Authors |
Robin Mesnage, Martina Biserni, Sucharitha Balu, Clément Frainay, Nathalie Poupin, Fabien Jourdan, Eva Wozniak, Theodoros Xenakis, Charles A. Mein, Michael N. Antoniou |
| Abstract |
Chemical pollutant exposure is a risk factor contributing to the growing epidemic of non-alcoholic fatty liver disease (NAFLD) affecting human populations that consume a western diet. Although it is recognized that intoxication by chemical pollutants can lead to NAFLD, there is limited information available regarding the mechanism by which typical environmental levels of exposure can contribute to the onset of this disease. Here, we describe the alterations in gene expression profiles and metabolite levels in the human HepaRG liver cell line, a validated model for cellular steatosis, exposed to the polychlorinated biphenyl (PCB) 126, one of the most potent chemical pollutants that can induce NAFLD. Sparse partial least squares classification of the molecular profiles revealed that exposure to PCB 126 provoked a decrease in polyunsaturated fatty acids as well as an increase in sphingolipid levels, concomitant with a decrease in the activity of genes involved in lipid metabolism. This was associated with an increased oxidative stress reflected by marked disturbances in taurine metabolism. A gene ontology analysis showed hallmarks of an activation of the AhR receptor by dioxin-like compounds. These changes in metabolome and transcriptome profiles were observed even at the lowest concentration (100 pM) of PCB 126 tested. A decrease in docosatrienoate levels was the most sensitive biomarker. Overall, our integrated multi-omics analysis provides mechanistic insight into how this class of chemical pollutant can cause NAFLD. Our study lays the foundation for the development of molecular signatures of toxic effects of chemicals causing fatty liver diseases to move away from a chemical risk assessment based on in vivo animal experiments. |
X Demographics
The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 50% |
| Unknown | 1 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 2 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 104 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 104 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 25 | 24% |
| Researcher | 20 | 19% |
| Student > Master | 10 | 10% |
| Student > Bachelor | 7 | 7% |
| Other | 7 | 7% |
| Other | 11 | 11% |
| Unknown | 24 | 23% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 21 | 20% |
| Medicine and Dentistry | 11 | 11% |
| Agricultural and Biological Sciences | 7 | 7% |
| Environmental Science | 6 | 6% |
| Pharmacology, Toxicology and Pharmaceutical Science | 6 | 6% |
| Other | 22 | 21% |
| Unknown | 31 | 30% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 09 August 2019.
All research outputs
#18,640,437
of 23,092,602 outputs
Outputs from Archives of Toxicology
#2,208
of 2,654 outputs
Outputs of similar age
#253,732
of 328,571 outputs
Outputs of similar age from Archives of Toxicology
#23
of 38 outputs
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