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Cell biology/molecular biology

Dechlorane Plus increases adipogenesis in 3T3-L1 and human primary preadipocytes independent of peroxisome proliferator-activated receptor γ transcriptional activity

International Journal of Obesity volume 43, pages 545–555 (2019)Cite this article

Subjects

Abstract

Background/objectives

Polybrominated diphenyl ethers (PBDEs) are chemicals that were added to consumer products to reduce flammability but were deemed toxic and bioaccumulative and were phased out of commerce. Flame retardants (FRs) such as Dechlorane Plus (DP) were introduced as replacements. DP is being produced in high volumes and is detected in the environment, human milk, and human serum. Although human exposure to DP is evident, little is known about its potential effects on human health. We and others have shown that some FRs are potential obesogens, i.e., promote adipogenesis. However, the effects of DP on adipogenesis are not known.

Methods

Murine 3T3-L1 and human primary subcutaneous (Sc) and omental (Om) preadipocytes were differentiated in the presence of DP (0.001–10 µM) and adipogenic effects were measured. Further, the ability of DP to activate the adipogenic transcription factor peroxisome proliferator-activated receptor γ (PPARγ) was also assessed.

Results

We show that treatment of murine preadipocytes with DP significantly (p < 0.05) increased lipid accumulation (2.5-fold) and the mRNA expression of adipogenic markers: fatty acid binding protein 4 (Fabp4), lipoprotein lipase (Lpl), perilipin (Plin), adipsin, and adiponectin. DP also significantly (p < 0.05) increased the protein levels of selected mature adipocyte markers. We further show using luciferase reporter assays that DP increased PPARγ transcriptional activity by threefold (p < 0.05). When the PPARγ agonist was replaced by DP in the human preadipocyte differentiation cocktail, DP significantly (p < 0.05) increased the mRNA levels of adipogenic markers, PPARγ, FABP4, and PLIN in human Sc as well as Om cultures. Finally, PPARγ antagonist studies revealed that DP-mediated upregulation of adipogenic markers Fabp4 and Lpl did not occur via PPARγ activation.

Conclusion

The current study shows that DP can induce adipogenesis of murine and human preadipocytes. We show that, although DP can directly activate PPARγ, its adipogenic effects may be mediated via other pathways.

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Acknowledgements

Thank you to the patients and surgeons of The Ottawa Hospital for human adipose tissue samples.

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Authors and Affiliations

  1. Environmental Health Science and Research Bureau, Health Canada, 50 Colombine Driveway, Ottawa, ON, Canada

    Vian Peshdary, Gabriella Calzadilla & Ella Atlas

  2. Ottawa Hospital Research Institute and Departments of Medicine and of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, ON, Canada

    Vian Peshdary, Alexander Sorisky & Ella Atlas

  3. Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada

    Anne Landry & Alexander Sorisky

Authors
  1. Vian Peshdary
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Correspondence to Ella Atlas.

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Peshdary, V., Calzadilla, G., Landry, A. et al. Dechlorane Plus increases adipogenesis in 3T3-L1 and human primary preadipocytes independent of peroxisome proliferator-activated receptor γ transcriptional activity. Int J Obes 43, 545–555 (2019). https://doi.org/10.1038/s41366-018-0072-7

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