Journal article
PCB126 blocks the thermogenic beiging response of adipocytes
Environmental science and pollution research international, Vol.27(9), pp.8897-8904
03/2020
DOI: 10.1007/s11356-019-06663-0
PMCID: PMC7098842
PMID: 31721030
Abstract
Subcutaneous white adipose tissue is capable of becoming thermogenic in a process that is referred to as "beiging." Beiging is associated with activation of the uncoupling protein, UCP1, and is known to be important for preventing adipose hypertrophy and development of insulin resistance. Polychlorinated biphenyls (PCBs) accumulate in fat, and it is hypothesized that disruption of adipogenesis and adipocyte function by PCBs may be causative in the development of obesity and diabetes. We developed immortal human subcutaneous preadipocytes that, when differentiated, are capable of beiging. Preadipocytes that were treated with polychlorinated biphenyl congener 126 (PCB126), followed by differentiation, were suppressed for their ability to activate UCP1 upon β-adrenergic stimulation with norepinephrine (NE), demonstrating a block in the beiging response. Treatment of preadipocytes with another known endogenous AhR agonist, indoxyl sulfate (IS), followed by differentiation also blocked the NE-stimulated upregulation of UCP1. Knockdown of the aryl hydrocarbon receptor (AhR) caused the preadipocytes to be refractory to PCB126 and IS effects. The chemical AhR antagonist, CH223191, was effective at preventing the effects of PCB126 but not IS, indicating AhR ligand specificity of CH223191. Repression of NE-induced UCP1 upregulation was also observed when already-differentiated mature adipocytes were treated with PCB126 but not IS. These results indicate that exposure of preadipocytes to endogenous (IS) or exogenous (PCB126) AhR agonists is effective at blocking them from becoming functional adipocytes that are capable of the beiging response. Mature adipocytes may have differential responses. This finding suggests a mechanism by which dioxin-like PCBs such as PCB126 could lead to disruption in energy homeostasis, potentially leading to obesity and diabetes.
Details
- Title: Subtitle
- PCB126 blocks the thermogenic beiging response of adipocytes
- Creators
- Francoise A Gourronc - Department of Microbiology and Immunology, University of Iowa, 3-612 BSB, 51 Newton Road, Iowa City, IA, 52242, USAGary H Perdew - Center for Molecular Toxicology and Carcinogenesis and the Department of Veterinary and Biomedical Sciences, Pennsylvania State University, University Park, 16802, PA, USALarry W Robertson - Department of Occupational & Environmental Health, College of Public Health, University of Iowa, Iowa City, IA, 52242, USAAloysius J Klingelhutz - Department of Microbiology and Immunology, University of Iowa, 3-612 BSB, 51 Newton Road, Iowa City, IA, 52242, USA. al-klingelhutz@uiowa.edu
- Resource Type
- Journal article
- Publication Details
- Environmental science and pollution research international, Vol.27(9), pp.8897-8904
- DOI
- 10.1007/s11356-019-06663-0
- PMID
- 31721030
- PMCID
- PMC7098842
- NLM abbreviation
- Environ Sci Pollut Res Int
- ISSN
- 1614-7499
- eISSN
- 1614-7499
- Publisher
- Germany
- Grant note
- P30 ES005605 / NIEHS NIH HHS P30 ES05605 / NIEHS NIH HHS R01 ES004869 / NIEHS NIH HHS P42 ES013661 / NIEHS NIH HHS P30 CA086862 / NCI NIH HHS
- Language
- English
- Date published
- 03/2020
- Academic Unit
- Microbiology and Immunology; Occupational and Environmental Health; Radiation Oncology
- Record Identifier
- 9984001183202771
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