Tributyltin promoted hepatic steatosis in zebrafish (Danio rerio) and the molecular pathogenesis involved

Aquat Toxicol. 2016 Jan;170:208-215. doi: 10.1016/j.aquatox.2015.11.028. Epub 2015 Dec 2.

Abstract

Endocrine disruptor effects of tributyltin (TBT) are well established in fish. However, the adverse effects on lipid metabolism are less well understood. Since the liver is the predominant site of de novo synthesis of lipids, the present study uses zebrafish (Danio rerio) to examine lipid accumulation in the livers and hepatic gene expression associated with lipid metabolism pathways. After exposure for 90 days, we found that the livers in fish exposed to TBT were yellowish in appearance and with accumulation of lipid droplet, which is consistent with the specific pathological features of steatosis. Molecular analysis revealed that TBT induced hepatic steatosis by increasing the gene expression associated with lipid transport, lipid storage, lipiogenic enzymes and lipiogenic factors in the livers. Moreover, TBT enhanced hepatic caspase-3 activity and up-regulated genes related to apoptosis and cell-death, which indicated steatotic livers of fish exposed to TBT and the subsequent liver damage were likely due to accelerated hepatocyte apoptosis or cell stress. In short, TBT can produce multiple and complex alterations in transcriptional activity of lipid metabolism and cell damage, which provides potential molecular evidence of TBT on hepatic steatosis.

Keywords: Hepatic steatosis; Lipid accumulation; Lipid metabolism; Tributyltin; Zebrafish.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Caspase 3 / metabolism
  • Fatty Liver / genetics*
  • Fatty Liver / pathology
  • Gene Expression Regulation / drug effects
  • Lipid Metabolism / drug effects
  • Lipid Metabolism / genetics
  • Lipids / analysis
  • Liver / drug effects
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Tin / analysis
  • Trialkyltin Compounds / toxicity*
  • Water Pollutants, Chemical / toxicity
  • Zebrafish / growth & development
  • Zebrafish / metabolism*

Substances

  • Lipids
  • Trialkyltin Compounds
  • Water Pollutants, Chemical
  • tributyltin
  • Tin
  • Caspase 3