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

• Published in: International Journal of Obesity Vol. 43; no. 3; p. 545
• Main Authors: Peshdary, Vian, Calzadilla, Gabriella, Landry, Anne, Sorisky, Alexander, Atlas, Ella
• Format: Journal Article
• Language: English
• Published: Nature Publishing Group 01-03-2019
• Subjects: Adipocytes; Cell differentiation; Consumer goods; Fatty acids; Flame retardants; Genetic aspects; Health aspects; Lipase; Lipoprotein lipase; Luciferase; Messenger RNA; Milk; Obesity; Protein binding; Risk factors; RNA; Transcription (Genetics)
• ISSN: 0307-0565
• DOI: 10.1038/s41366-018-0072-7

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 [micro]M) and adipogenic effects were measured. Further, the ability of DP to activate the adipogenic transcription factor peroxisome proliferator-activated receptor [gamma] (PPAR[gamma]) 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 PPAR[gamma] transcriptional activity by threefold (p < 0.05). When the PPAR[gamma] agonist was replaced by DP in the human preadipocyte differentiation cocktail, DP significantly (p < 0.05) increased the mRNA levels of adipogenic markers, PPAR[gamma], FABP4, and PLIN in human Sc as well as Om cultures. Finally, PPAR[gamma] antagonist studies revealed that DP-mediated upregulation of adipogenic markers Fabp4 and Lpl did not occur via PPAR[gamma] activation. Conclusion The current study shows that DP can induce adipogenesis of murine and human preadipocytes. We show that, although DP can directly activate PPAR[gamma], its adipogenic effects may be mediated via other pathways.