Hydroxylation markedly alters how the polychlorinated biphenyl (PCB) congener, PCB52, affects gene expression in human preadipocytes

Francoise A. Gourronc; Michael S. Chimenti; Hans-Joachim Lehmler; James A. Ankrum; Aloysius J. Klingelhutz

doi:10.1016/j.tiv.2023.105568

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Hydroxylation markedly alters how the polychlorinated biphenyl (PCB) congener, PCB52, affects gene expression in human preadipocytes

Journal article

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Hydroxylation markedly alters how the polychlorinated biphenyl (PCB) congener, PCB52, affects gene expression in human preadipocytes

Francoise A. Gourronc, Michael S. Chimenti, Hans-Joachim Lehmler, James A. Ankrum and Aloysius J. Klingelhutz

Toxicology in vitro, Vol.89, 105568

06/2023

DOI: 10.1016/j.tiv.2023.105568

PMCID: PMC10081964

PMID: 36804509

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https://pmc.ncbi.nlm.nih.gov/articles/PMC10081964/pdf/nihms-1874746.pdfView

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Abstract

Polychlorinated biphenyls (PCBs) accumulate in adipose tissue and are linked to obesity and diabetes. The congener, PCB52 (2,2′,5,5′-tetrachorobiphenyl), is found at high levels in school air. Hydroxylation of PCB52 to 4-OH-PCB52 (4-hydroxy-2,2′,5,5′-tetrachorobiphenyl) may increase its toxicity. To understand PCB52's role in causing adipose dysfunction, we exposed human preadipocytes to PCB52 or 4-OH-PCB52 across a time course and assessed transcript changes using RNAseq. 4-OH-PCB52 caused considerably more changes in the number of differentially expressed genes as compared to PCB52. Both PCB52 and 4-OH-PCB52 upregulated transcript levels of the sulfotransferase SULT1E1 at early time points, but cytochrome P450 genes were generally not affected. A set of genes known to be transcriptionally regulated by PPARα were consistently downregulated by PCB52 at all time points. In contrast, 4-OH-PCB52 affected a variety of pathways, including those involving cytokine responses, hormone responses, focal adhesion, Hippo, and Wnt signaling. Sets of genes known to be transcriptionally regulated by IL17A or parathyroid hormone (PTH) were found to be consistently downregulated by 4-OH-PCB52. Most of the genes affected by PCB52 and 4-OH-PCB52 were different and, of those that were the same, many were changed in an opposite direction. These studies provide insight into how PCB52 or its metabolites may cause adipose dysfunction to cause disease. •RNAseq was performed on human preadipocytes exposed to PCB52 or 4-OH-PCB52.•4-OH-PCB52 caused considerably more changes in gene expression than PCB52.•PCB52 or 4-OH-PCB52 often caused gene expression changes in opposite direction.•PCB52 inhibited expression of genes involved in the PPARa pathway.•4-OH-PCB52 altered genes in cytokine, hormone, focal adhesion, and Wnt pathways.

Diabetes

Inflammation

Obesity

Adipose

PCB52

Preadipocytes

RNAseq

Details

Title: Subtitle: Hydroxylation markedly alters how the polychlorinated biphenyl (PCB) congener, PCB52, affects gene expression in human preadipocytes
Creators: Francoise A. Gourronc - University of Iowa
Michael S. Chimenti - University of Iowa
Hans-Joachim Lehmler - University of Iowa
James A. Ankrum - University of Iowa
Aloysius J. Klingelhutz - Department of Microbiology and Immunology, University of Iowa, United States
Resource Type: Journal article
Publication Details: Toxicology in vitro, Vol.89, 105568
DOI: 10.1016/j.tiv.2023.105568
PMID: 36804509
PMCID: PMC10081964
NLM abbreviation: Toxicol In Vitro
ISSN: 0887-2333
eISSN: 1879-3177
Publisher: Elsevier Ltd
Language: English
Date published: 06/2023
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Microbiology and Immunology; Occupational and Environmental Health; Iowa Neuroscience Institute; Radiation Oncology; Fraternal Order of Eagles Diabetes Research Center; Iowa Superfund Research Program; Iowa Institute of Human Genetics
Record Identifier: 9984368431902771

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