Halogenated bisphenol-a analogs act as obesogens in zebrafish larvae (Danio rerio)

Anne Riu, Catherine W. Mccollum, Caroline L. Pinto, Marina Grimaldi, Anne Hillenweck, Elisabeth Perdu, Daniel Zalko, Laure Bernard, Vincent Laudet, Patrick Balaguer, Maria Bondesson, Jan Ake Gustafsson

Research output: Contribution to journalArticlepeer-review

95 Scopus citations


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.

Original languageEnglish (US)
Article numberkfu036
Pages (from-to)48-58
Number of pages11
JournalToxicological Sciences
Issue number1
StatePublished - Apr 2014


  • Lipid
  • Obesity
  • PPARγ
  • Zebrafish

ASJC Scopus subject areas

  • Toxicology


Dive into the research topics of 'Halogenated bisphenol-a analogs act as obesogens in zebrafish larvae (Danio rerio)'. Together they form a unique fingerprint.

Cite this