Transcriptome sequencing of 3, 3′, 4, 4′, 5-Pentachlorobiphenyl (PCB126)-treated human preadipocytes demonstrates progressive changes in pathways associated with inflammation and diabetes. (September 2022)

• Record Type: Journal Article
• Authors: Gourronc, Francoise A.; Helm, Brynn K.; Robertson, Larry W.; Chimenti, Michael S.; Joachim-Lehmler, Hans; Ankrum, James A.; Klingelhutz, Aloysius J.
• Is Part Of: Toxicology in vitro. Volume 83(2022)
• Publication Date: 2022-09
• Subjects: Polychlorinated biphenyls -- PCB126 -- Adipose -- AhR -- RNAseq -- Inflammation; Toxicity testing -- In vitro -- Periodicals; Toxicology -- Periodicals; 615.9
• DOI: 10.1016/j.tiv.2022.105396
• Languages: English
• ISSNs: 0887-2333

Abstract

Abstract: Polychlorinated biphenyls (PCBs) are persistent organic pollutants that accumulate in adipose tissue and have been associated with cardiometabolic disease. We have previously demonstrated that exposure of human preadipocytes to the dioxin-like PCB126 disrupts adipogenesis via the aryl hydrocarbon receptor (AhR). To further understand how PCB126 disrupts adipose tissue cells, we performed RNAseq analysis of PCB126-treated human preadipocytes over a 3-day time course. The most significant predicted upstream regulator affected by PCB126 exposure at the early time point of 9 h was the AhR. Progressive changes occurred in the number and magnitude of transcript levels of genes associated with inflammation, most closely fitting the pathways of cytokine-cytokine-receptor signaling and the AGE-RAGE diabetic complications pathway. Transcript levels of genes involved in the IL-17A, IL-1β, MAP kinase, and NF-κB signaling pathways were increasingly dysregulated by PCB126 over time. Our results illustrate the progressive time-dependent nature of transcriptional changes caused by toxicants such as PCB126, point to important pathways affected by PCB126 exposure, and provide a rich dataset for further studies to address how PCB126 and other AhR agonists disrupt preadipocyte function. These findings have implications for understanding how dioxin-like PCBs and other dioxin-like compounds are involved in the development of obesity and diabetes. Graphical abstract: Unlabelled Image Highlights: PCB126 causes progressive changes in the number and magnitude of gene transcripts associated with AhR and cytokine-cytokine-receptor signaling. IL17A, IL-1β, and the AGE-RAGE diabetic complications pathways are activated by PCB126 in human preadipocytes. A rich data set is provided for further studies on how PCB126 and other AhR agonists disrupt preadipocyte function to cause metabolic disease.