The Mammalian "Obesogen" Tributyltin Targets Hepatic Triglyceride Accumulation and the Transcriptional Regulation of Lipid Metabolism in the Liver and Brain of Zebrafish

PLoS One. 2015 Dec 3;10(12):e0143911. doi: 10.1371/journal.pone.0143911. eCollection 2015.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipogenesis / drug effects
  • Adipogenesis / physiology
  • Animals
  • Brain / drug effects*
  • Brain / metabolism
  • Lipid Metabolism / drug effects*
  • Lipid Metabolism / physiology
  • Liver / drug effects*
  • Liver / metabolism
  • Transcriptional Activation / drug effects
  • Transcriptional Activation / physiology
  • Trialkyltin Compounds / pharmacology*
  • Triglycerides / metabolism*
  • Zebrafish

Substances

  • Trialkyltin Compounds
  • Triglycerides
  • tributyltin

Grants and funding

This work was supported by FCT-Fundação para a Ciência e a Tecnologia (Portugal), through project PTDC/MAR/115199/2009, the European Regional Development Fund (ERDF) through the COMPETE—Operational Competitiveness Programme and national funds through FCT – Fundação para a Ciência e a Tecnologia, under the project “PEst-C/MAR/LA0015/2013” and pos-doctoral fellowship SFRH/BPD/74231/2010. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.