Halogenated Bisphenol-A Analogs Act as Obesogens in Zebrafish Larvae (Danio rerio)

Abstract

Obesity has increased dramatically over the past decades, reaching epidemic proportions. The reasons are likely multifactorial. One of the suggested causes is the accelerated exposure to obesity-inducing chemicals (obesogens). However, out of the tens of thousands of industrial chemicals humans are exposed to, very few have been tested for their obesogenic potential, mostly due to the limited availability of appropriate in vivo screening models. In this study, we investigated whether two commonly used flame retardants, the halogenated bisphenol-A (BPA) analogs tetrabromobisphenol-A (TBBPA) and tetrachlorobisphenol-A (TCBPA), could act as obesogens using zebrafish larvae as an in vivo animal model. The effect of embryonic exposure to these chemicals on lipid accumulation was analyzed by Oil Red-O staining, and correlated to their capacity to activate human and zebrafish peroxisome proliferator-activated receptor gamma (PPARγ) in zebrafish and in reporter cell lines. Then, the metabolic fate of TBBPA and TCBPA in zebrafish larvae was analyzed by high-performance liquid chromatography (HPLC) . TBBPA and TCBPA were readily taken up by the fish embryo and both compounds were biotransformed to sulfate-conjugated metabolites. Both halogenated-BPAs, as well as TBBPA-sulfate induced lipid accumulation in zebrafish larvae. TBBPA and TCBPA also induced late-onset weight gain in juvenile zebrafish. These effects correlated to their capacity to act as zebrafish PPARγ agonists. Screening of chemicals for inherent obesogenic capacities through the zebrafish lipid accumulation model could facilitate prioritizing chemicals for further investigations in rodents, and ultimately, help protect humans from exposure to environmental obesogens.

Lxr regulates lipid metabolic and visual perception pathways during zebrafish development

“…The clones with best induction factor were selected and expanded in culture in the presence of 0.5 μg/mL puromycin. Generation of luciferase reporter cells expressing zebrafish Pparγ (HG5LN-zfPparγ cells) has been described previously (18) .…”

Steroid modulation of neurogenesis: Focus on radial glial cells in zebrafish

“…Alterations of heart morphology, skeletal muscles organizations have been described in early-life BPAtreated zebrafish [125][126][127][128]. A recent study showed that zebrafish embryos exposed to BPA accumulate lipids, suggesting a role of BPA in the onset of overweight and obesity [129]. Centrally BPA treatments elicit an upregulation of AroB expression in zebrafish larvae [130,131], an estrogenic effect mediated by estrogen receptor binding and transcriptional activation [124].…”

Alteration of cellular lipids and lipid metabolism markers in RTL-W1 cells exposed to model endocrine disrupters

“…Also, long term exposure to TBT induced lipid and fatty acid accumulation in the ramshorn snail Marisa cornuarietis (Janer et al, 2007). TBT, tetrabromobisphenol-A (TTBPA), tetrachlorobisphenol-A and TTBPA-sulfate induced lipid accumulation in zebrafish larvae, which are proposed as a screening model (Tingaud-Sequeira et al, 2011;Riu et al, 2014).…”