title: The Mammalian "Obesogen" Tributyltin Targets Hepatic Triglyceride Accumulation and the Transcriptional Regulation of Lipid Metabolism in the Liver and Brain of Zebrafish.
abstract: Recent findings indicate that different Endocrine Disrupting Chemicals (EDCs) interfere with lipid metabolic pathways in mammals and promote fat accumulation, a previously unknown site of action for these compounds. The antifoulant and environmental pollutant tributyltin (TBT), which causes imposex in gastropod snails, induces an "obesogenic" phenotype in mammals, through the activation of the nuclear receptors retinoid X receptor (RXR) and peroxisome proliferator-activated receptor gamma (PPARγ). In teleosts, the effects of TBT on the lipid metabolism are poorly understood, particularly following exposure to low, environmental concentrations. In this context, the present work shows that exposure of zebrafish to 10 and 50 ng/L of TBT (as Sn) from pre-hatch to 9 months of age alters the body weight, condition factor, hepatosomatic index and hepatic triglycerides in a gender and dose related manner. Furthermore, TBT modulated the transcription of key lipid regulating factors and enzymes involved in adipogenesis, lipogenesis, glucocorticoid metabolism, growth and development in the brain and liver of exposed fish, revealing sexual dimorphic effects in the latter. Overall, the present study shows that the model mammalian obesogen TBT interferes with triglyceride accumulation and the transcriptional regulation of lipid metabolism in zebrafish and indentifies the brain lipogenic transcription profile of fish as a new target of this compound.
authors.affiliation: CIMAR/CIIMAR-AL, Interdisciplinary Centre of Marine and Environmental Research, Rua dos Bragas 289, 4050-123, Porto, Portugal.
authors.forename: Angeliki
authors.initials: A
authors.lastname: Lyssimachou
authors.affiliation: CIMAR/CIIMAR-AL, Interdisciplinary Centre of Marine and Environmental Research, Rua dos Bragas 289, 4050-123, Porto, Portugal.
authors.forename: Joana G
authors.initials: JG
authors.lastname: Santos
authors.affiliation: CIMAR/CIIMAR-AL, Interdisciplinary Centre of Marine and Environmental Research, Rua dos Bragas 289, 4050-123, Porto, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: André
authors.affiliation: CIMAR/CIIMAR-AL, Interdisciplinary Centre of Marine and Environmental Research, Rua dos Bragas 289, 4050-123, Porto, Portugal.
authors.forename: Joana
authors.initials: J
authors.lastname: Soares
authors.affiliation: CIMAR/CIIMAR-AL, Interdisciplinary Centre of Marine and Environmental Research, Rua dos Bragas 289, 4050-123, Porto, Portugal.
authors.forename: Daniela
authors.initials: D
authors.lastname: Lima
authors.affiliation: CIMAR/CIIMAR-AL, Interdisciplinary Centre of Marine and Environmental Research, Rua dos Bragas 289, 4050-123, Porto, Portugal.
authors.forename: Laura
authors.initials: L
authors.lastname: Guimarães
authors.affiliation: CIMAR/CIIMAR-AL, Interdisciplinary Centre of Marine and Environmental Research, Rua dos Bragas 289, 4050-123, Porto, Portugal.
authors.forename: C Marisa R
authors.initials: CM
authors.lastname: Almeida
authors.affiliation: CIMAR/CIIMAR-AL, Interdisciplinary Centre of Marine and Environmental Research, Rua dos Bragas 289, 4050-123, Porto, Portugal.
authors.forename: Catarina
authors.initials: C
authors.lastname: Teixeira
authors.affiliation: CIMAR/CIIMAR-AL, Interdisciplinary Centre of Marine and Environmental Research, Rua dos Bragas 289, 4050-123, Porto, Portugal.
authors.forename: L Filipe C
authors.initials: LF
authors.lastname: Castro
authors.affiliation: CIMAR/CIIMAR-AL, Interdisciplinary Centre of Marine and Environmental Research, Rua dos Bragas 289, 4050-123, Porto, Portugal.|FCUP-Department of Biology, Faculty of Sciences, University of Porto, Porto, Portugal.
authors.forename: Miguel M
authors.initials: MM
authors.lastname: Santos
mesh_terms: D050156:Adipogenesis / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects* / Q000502:physiology; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects / Q000502:physiology; D014220:Trialkyltin Compounds / Q000494:pharmacology*; D014280:Triglycerides / Q000378:metabolism*; D015027:Zebrafish
chemical_list: D014220:Trialkyltin Compounds; D014280:Triglycerides; C011559:tributyltin