Tributyltin chloride leads to adiposity and impairs metabolic functions in the rat liver and pancreas

Toxicol Lett. 2015 May 19;235(1):45-59. doi: 10.1016/j.toxlet.2015.03.009. Epub 2015 Mar 25.

Abstract

Tributyltin chloride (TBT) is an environmental contaminant used in antifouling paints of boats. Endocrine disruptor effects of TBT are well established in animal models. However, the adverse effects on metabolism are less well understood. The toxicity of TBT in the white adipose tissue (WAT), liver and pancreas of female rats were assessed. Animals were divided into control and TBT (0.1 μg/kg/day) groups. TBT induced an increase in the body weight of the rats by the 15th day of oral exposure. The weight gain was associated with high parametrial (PR) and retroperitoneal (RP) WAT weights. TBT-treatment increased the adiposity, inflammation and expression of ERα and PPARγ proteins in both RP and PR WAT. In 3T3-L1 cells, estrogen treatment reduced lipid droplets accumulation, however increased the ERα protein expression. In contrast, TBT-treatment increased the lipid accumulation and reduced the ERα expression. WAT metabolic changes led to hepatic inflammation, lipid accumulation, increase of PPARγ and reduction of ERα protein expression. Accordingly, there were increases in the glucose tolerance and insulin sensitivity tests with increases in the number of pancreatic islets and insulin levels. These findings suggest that TBT leads to adiposity in WAT specifically, impairing the metabolic functions of the liver and pancreas.

Keywords: Adiposity; Inflammation; Insulin; Liver; Pancreas; TBT chloride.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes, White / drug effects
  • Adipocytes, White / metabolism
  • Adipogenesis / drug effects
  • Adipose Tissue, White / drug effects*
  • Adipose Tissue, White / metabolism
  • Adipose Tissue, White / physiopathology
  • Adiposity / drug effects*
  • Animals
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Chemical and Drug Induced Liver Injury / etiology*
  • Chemical and Drug Induced Liver Injury / genetics
  • Chemical and Drug Induced Liver Injury / metabolism
  • Chemical and Drug Induced Liver Injury / physiopathology
  • Endocrine Disruptors / toxicity*
  • Environmental Pollutants / toxicity*
  • Estrogen Receptor alpha / genetics
  • Estrogen Receptor alpha / metabolism
  • Fatty Liver / chemically induced*
  • Fatty Liver / genetics
  • Fatty Liver / metabolism
  • Fatty Liver / physiopathology
  • Female
  • Insulin / blood
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / physiopathology
  • Mice
  • PPAR gamma / genetics
  • PPAR gamma / metabolism
  • Pancreas / drug effects*
  • Pancreas / metabolism
  • Pancreas / physiopathology
  • Rats, Wistar
  • Time Factors
  • Trialkyltin Compounds / toxicity*
  • Weight Gain

Substances

  • Blood Glucose
  • Endocrine Disruptors
  • Environmental Pollutants
  • Estrogen Receptor alpha
  • Insulin
  • PPAR gamma
  • Trialkyltin Compounds
  • tributyltin