Article Cite This: Environ. Sci. Technol. 2019, 53, 7830−7839
pubs.acs.org/est
Tributyltin Affects Retinoid X Receptor-Mediated Lipid Metabolism in the Marine Rotifer Brachionus koreanus Min-Chul Lee,†,# Elza Fonseca,‡,§,# Jun Chul Park,† Deok-Seo Yoon,† Hyuntae Choi,∥ Moonkoo Kim,⊥,# Jeonghoon Han,† Hyeon-Seo Cho,¶ Kyung-Hoon Shin,∥ Miguel L. Santos,‡,§ Jee-Hyun Jung,⊥,# L. Filipe C. Castro,‡,§ and Jae-Seong Lee*,† †
Department of Biological Science, College of Science, Sungkyunkwan University, Suwon 16419, South Korea Department of Biology, Faculty of Sciences, University of Porto, 4169-007 Porto, Portugal § Interdisciplinary Centre of Marine and Environmental Research, University of Porto, 4450-208 Matosinhos, Portugal ∥ Department of Marine and Convergence Sciences, College of Science and Technology, Hanyang University, Ansan 15588, South Korea ⊥ Risk Assessment Research Center, Korea Institute of Ocean Science & Technology, Geoje 53201, South Korea # Department of Marine Environmental Science, Korea University of Science and Technology, Daejeon 34113, South Korea ¶ College of Fisheries and Ocean Sciences, Chonnam National University, Yeosu 550-749, South Korea
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S Supporting Information *
ABSTRACT: To examine how tributyltin (TBT), a model obesogen, affects the lipid metabolism in the marine rotifer Brachionus koreanus, we carried out life-cycle studies and determined the in vitro and in silico interactions of retinoid X receptor (RXR) with TBT, the transcriptional levels of RXR and lipid metabolic genes, and the fatty acid content. The lethal concentration 10% (LC10) was determined to be 5.12 μg/L TBT, and negative effects on ecologically relevant end points (e.g., decreased lifespan and fecundity) were detected at 5 μg/L TBT. On the basis of these findings, subsequent experiments were conducted below 1 μg/L TBT, which did not show any negative effects on ecologically relevant end points in B. koreanus. Nile red staining analysis showed that after exposure to 1 μg/ L TBT, B. koreanus stored neutral lipids and had significantly increased transcriptional levels of RXR and lipid metabolism-related genes compared to the control. However, the content of total fatty acids did not significantly change at any exposure level. In the single fatty acids profile, a significant increase in saturated fatty acids (SFAs) 14:0 and 20:0 was observed, but the contents of omega-3 and omega-6 fatty acids were significantly decreased. Also, a transactivation assay of TBT with RXR showed that TBT is an agonist of Bk-RXR with a similar fold-induction to the positive control. Taken together, these results demonstrate that TBT-modulated RXR signaling leads to increase in transcriptional levels of lipid metabolismrelated genes and the synthesis of SFAs but decreases the content of polyunsaturated fatty acids (PUFAs). Our findings support a wider taxonomic scope of lipid perturbation due to xenobiotic exposure that occurs via NRs in aquatic animals.
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exposure.2−5 Organotins, such as tributyltin (TBT), are considered model obesogen compounds for which detailed mechanistic and physiological modes of action have been described. Since the 1960s, TBT has been widely used as biocide for agricultural purposes and as an antifouling paint for industrial processes including application to the hulls of ships to improve durability and performance.6,7 However, due to constant increase of TBT-induced noxious effects in the marine ecosystem, TBT has consequently been defined as “the
INTRODUCTION The endocrine system is a key regulator of energetic metabolism and plays an essential role in maintaining overall balance and organism homeostasis.1 Yet, due to anthropogenic activities, deleterious environmental chemicals have been widely released throughout the world’s ecosystems over recent decades. Endocrine-disrupting chemicals (EDCs) are a diverse range of compounds able to interfere with or alter regulatory endocrine modules, leading to physiological and reproductive impairment. A striking emerging example of the harmful effects caused by exposure to EDCs is the abnormal weight gain due to lipid metabolism disturbances. Additionally, disturbances in adipocyte differentiation and development and lipid accumulation have been described as biological end points of EDC © 2019 American Chemical Society
Received: Revised: Accepted: Published: 7830
March 4, 2019 June 3, 2019 June 5, 2019 June 5, 2019 DOI: 10.1021/acs.est.9b01359 Environ. Sci. Technol. 2019, 53, 7830−7839
Article
Environmental Science & Technology
distilled water to make 15-ppt, which was then filtered through a 45 um sieve. Tetraselmis suecica was used as the dietary source at a concentration of 6 × 104 cells/mL every 24 h, and the culture system was maintained under a 12 h/12 h (light:dark) photocycle at 25 °C. Acute Toxicity and Life Cycle Parameters. The acute toxicity of TBT in B. koreanus was assessed using neonates (ten per concentration); they were collected (
