title: Pharmacological evaluation of the mechanisms involved in increased adiposity in zebrafish triggered by the environmental contaminant tributyltin.
abstract: One proposed contributing factor to the rise in overweight and obesity is exposure to endocrine disrupting chemicals. Tributyltin chloride (TBT), an organotin, induces adipogenesis in cell culture models and may increases adipose mass in vivo in vertebrate model organisms. It has been hypothesized that TBT acts via the peroxisome proliferator activated receptor (PPAR)γ-dependent pathway. However, the mechanisms involved in the effects of TBT exposure on in vivo adipose tissue metabolism remain unexplored. Semitransparent zebrafish larvae, with their well-developed white adipose tissue, offer a unique opportunity for studying the effects of toxicant chemicals and pharmaceuticals on adipocyte biology and whole-organism adiposity in a vertebrate model. Within hours, zebrafish larvae, treated at environmentally-relevant nanomolar concentrations of TBT, exhibited a remarkable increase in adiposity linked to adipocyte hypertrophy. Under the experimental conditions used, we also demonstrated that zebrafish larvae adipose tissue proved to be highly responsive to selected human nuclear receptor agonists and antagonists. Retinoid X receptor (RXR) homodimers and RXR/liver X receptor heterodimers were suggested to be in vivo effectors of the obesogenic effect of TBT on zebrafish white adipose tissue. RXR/PPARγ heterodimers may be recruited to modulate adiposity in zebrafish but were not a necessary requirement for the short term in vivo TBT obesogenic effect. Together, the present results suggest that TBT may induce the promotion of triacylglycerol storage in adipocytes via RXR-dependent pathways without necessary using PPAR isoforms.
authors.affiliation: Maladies Rares: Génétique et Métabolisme (MRGM), Univ. Bordeaux, INSERM, U1211, F-33615 Pessac, France.
authors.forename: Nafia
authors.initials: N
authors.lastname: Ouadah-Boussouf
authors.affiliation: Maladies Rares: Génétique et Métabolisme (MRGM), Univ. Bordeaux, INSERM, U1211, F-33615 Pessac, France. Electronic address: p.babin@gpp.u-bordeaux1.fr.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Babin
mesh_terms: D017667:Adipocytes / Q000187:drug effects; D000273:Adipose Tissue / Q000187:drug effects; D052436:Adipose Tissue, White / Q000187:drug effects; D050154:Adiposity / Q000187:drug effects*; D000818:Animals; D048429:Cell Size / Q000187:drug effects; D004785:Environmental Pollutants / Q000633:toxicity*; D006801:Humans; D007814:Larva; D009765:Obesity / Q000139:chemically induced / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000037:antagonists & inhibitors; D047488:Retinoid X Receptors / Q000187:drug effects; D014220:Trialkyltin Compounds / Q000633:toxicity*; D015027:Zebrafish
chemical_list: D004785:Environmental Pollutants; D047495:PPAR gamma; D018160:Receptors, Cytoplasmic and Nuclear; D047488:Retinoid X Receptors; D014220:Trialkyltin Compounds; C011559:tributyltin
keywords: Adipocyte; Nuclear receptors; Obesity; Obesogen; Tributyltin chloride; Zebrafish