Induction of Adipocyte Differentiation by Polybrominated Diphenyl Ethers (PBDEs) in 3T3-L1 Cells

Abstract

Polybrominated diphenyl ethers (PBDEs) are a class of brominated flame retardants that were extensively used in commercial products. PBDEs are ubiquitous environmental contaminants that are both lipophilic and bioaccumulative. Effects of PBDEs on adipogenesis were studied in the 3T3-L1 preadipocyte cell model in the presence and absence of a known adipogenic agent, dexamethasone (DEX). A PBDE mixture designed to mimic body burden of North Americans was tested, in addition to the technical mixture DE-71 and the individual congener BDE-47. The mixture, DE-71, and BDE-47 all induced adipocyte differentiation as assessed by markers for terminal differentiation [fatty acid binding protein 4 (aP2) and perilipin] and lipid accumulation. Characterization of the differentiation process in response to PBDEs indicated that adipogenesis induced by a minimally effective dose of DEX was enhanced by these PBDEs. Moreover, C/EBPα, PPARγ, and LXRα were induced late in the differentiation process. Taken together, these data indicate that adipocyte differentiation is induced by PBDEs; they act in the absence of glucocorticoid and enhance glucocorticoid-mediated adipogenesis.

Adipose Tissue as a Site of Toxin Accumulation

“…Moreover, di(2-ethylhexyl) phthalate (DEHP) or its metabolite mono-(2-ethylhexyl) phthalate (MEHP) increased adipocyte differentiation in 3T3-L1 cells, (142) (115), murine mesenchymal stem cells (44), and in vivo (142) (62). Few human studies have addressed effects of BFRs on obesity and metabolic syndrome; however, adipocyte differentiation was increased by the BFRs PDBE (397) and BDE-47 (185). These findings are supported by a recent study which reported increased body weight of obese mice treated with hexabromocyclododecane (HBCD) (431).…”

Characterization of Adipogenic Activity of House Dust Extracts and Semi-Volatile Indoor Contaminants in 3T3-L1 Cells

“…Some of these chemicals have been previously assessed in 3T3-L1 cells, and agree with our results. BDE-47 has been previously reported to promote a low level of triglyceride accumulation 46–48 , chlorpyrifos has previously been demonstrated to increase body weight in vivo but not promote (and perhaps inhibit) differentiation in vitro 49, 50 , triclosan has been demonstrated to inhibit adipogenesis 51 , and fipronil has been demonstrated to exhibit minimal triglyceride accumulation 52 . Previous work has demonstrated a low level of triglyceride accumulation for several parabens 50, 53 , in apparent contrast with our results, though this occurred only at concentrations greater than those we tested.…”

Indoor and Outdoor Concentrations of Polybrominated Diphenyl Ethers on Respirable Particulate in Central and Southern Taiwan

“…However, with the lower vapor pressures of nona-and deca-BDEs, they are mostly particle-bound which makes them harder to degrade photochemically (Raff and Hites, 2007). Various equipment containing PBDEs found in the indoor environment are main sources of PBDE emission into the air via volatilization (Tung et al, 2014). The existence of these higher brominated PBDEs in the indoor air is probably attributed to their migration behaviours from outdoors to indoors.…”

“…PBDEs have been regarded as a major concern due to their ubiquitous existence in the environment (e.g., form the source to the surrounding air) and their harmful health effects. They are also highly resistant to biological, chemical, and physical degradation, and tend to bio accumulate easily due to their lipophilic property (Cincinelli et al, 2014;Tung et al, 2014). PBDEs negatively affect the endocrine and reproductive functions of humans most especially in females (Hood, 2006;Shy et al, 2012) and cause neurodevelopmental delays after neonatal ingestion of breast milk with high PBDE level (Lin et al, 2010;Chao et al, 2011;Shy et al, 2011;Gascon et al, 2012;Shy et al, 2012).…”