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.
Highlights
The lipid metabolism as a target of Endocrine Disrupting Chemicals (EDCs) is a recent field in endocrine disruption research
The present work demonstrates that the mammalian “obesogen” TBT -reported to increase adipose mass and induce non-alcoholic fatty liver disease (NAFLD) in mammals through the activation of PPARγ and retinoid X receptor (RXR) [17,18,19]- perturbs the energy reserves and transcriptional regulation of lipid metabolism in the model teleost zebrafish following chronic exposure to very low and environmentally relevant concentrations
In male fish exposed to 50 ng/L TBT, the increase in the up-regulation of the de novo lipogenesis genes sterol regulatory element-binding protein 1 (SREBP1) and fatty acid synthase (FASn) didn’t result in the production of more triglycerides
Summary
Infinity Triglycerides Liquid Stable Reagent was purchased from ThermoScientific. Tributyltin Chloride (TBTCl; 96% purity) and all other reagents were obtained from Sigma-Aldrich unless stated otherwise in the text. The fish were fed ad libitum twice a day with a commercial fish diet Tetramin (Tetra, Melle, Germany) and supplemented with live brine shrimp (Artemia spp.). In the afternoon before breeding, two random groups of 4–6 males and 10–12 females were transferred in net cages doi:10.1371/journal.pone.0143911.g001 bottom-covered with glass marbles, placed within 30 L aquaria and fed just with live brine shrimp (Artemia spp.). The morning (1.5 hour after sunlight) breeding fish were removed, the eggs were collected from the bottom of the tank by siphoning, cleaned in egg water and randomly allocated to experimental aquaria
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