ArticlePloS one2019
Tributyltin chloride (TBT) induces RXRA down-regulation and lipid accumulation in human liver cells.
Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 40 citations in OpenAlex.
- Tributyltin induces conjugation of ATG8s to single membranes via the V-ATPase-ATG16L1 axis, leading to transcription factor EB activation in human cell lines.Archives of toxicology · 2026Article
- Obesogens in Prostate Cancer: An Endocrine and Metabolic Threat.Current obesity reports · 2026Review
- Exploring the mechanism of PFTrDA on human hepatic metabolic diseases based on network toxicology and molecular docking.Scientific reports · 2025Article
- Overview of the hazardous impacts of metabolism-disrupting chemicals on the progression of fatty liver diseases.Molecular & cellular toxicology · 2025Article
- Environmental Obesogens and Their Perturbations in Lipid Metabolism.Environment & health (Washington, D.C.) · 2024Review
- Addressing chemically-induced obesogenic metabolic disruption: selection of chemicals forFrontiers in endocrinology · 2024Review
- Long non-coding RNA HOX transcript antisense intergenic RNA depletion protects against alcoholic hepatitis through the microRNA-148a-3p/sphingosine 1-phosphate receptor 1 axis.Cell and tissue research · 2023Article
- Origin, dietary exposure, and toxicity of endocrine-disrupting food chemical contaminants: A comprehensive review.Heliyon · 2023Article
- Sex, Nutrition, and NAFLD: Relevance of Environmental Pollution.Nutrients · 2023Review
- Inherited Epigenetic Hallmarks of Childhood Obesity Derived from Prenatal Exposure to Obesogens.International journal of environmental research and public health · 2023Review
- Metabolism-Disrupting Chemicals Affecting the Liver: Screening, Testing, and Molecular Pathway Identification.International journal of molecular sciences · 2023Review
- A Novel in Duck Myoblasts: The Transcription Factor Retinoid X Receptor Alpha (RXRA) Inhibits Lipid Accumulation by Promoting CD36 Expression.International journal of molecular sciences · 2023Article
- Application of In Vitro Models for Studying the Mechanisms Underlying the Obesogenic Action of Endocrine-Disrupting Chemicals (EDCs) as Food Contaminants-A Review.International journal of molecular sciences · 2023Review
- Integrated analysis of mRNA-seq and miRNA-seq reveals the potential roles of Egr1, Rxra and Max in kidney stone disease.Urolithiasis · 2022Article
- Obesity II: Establishing causal links between chemical exposures and obesity.Biochemical pharmacology · 2022Review
- Inferring mammalian tissue-specific regulatory conservation by predicting tissue-specific differences in open chromatin.BMC genomics · 2022Article
- Associations Between Serum Multiple Metals Exposures and Metabolic Syndrome: a Longitudinal Cohort Study.Biological trace element research · 2021Article
- The GOLIATH Project: Towards an Internationally Harmonised Approach for Testing Metabolism Disrupting Compounds.International journal of molecular sciences · 2020Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
A subset of environmental chemicals acts as "obesogens" as they increase adipose mass and lipid content in livers of treated rodents. One of the most studied class of obesogens are the tin-containing chemicals that have as a central moiety tributyltin (TBT), which bind and activate two nuclear hormone receptors, Peroxisome Proliferator Activated Receptor Gamma (PPARG) and Retinoid X Receptor Alpha (RXRA), at nanomolar concentrations. Here, we have tested whether TBT chloride at such concentrations may affect the neutral lipid level in two cell line models of human liver. Indeed, using high content image analysis (HCA), TBT significantly increased neutral lipid content in a time- and concentration-dependent manner. Consistent with the observed increased lipid accumulation, RNA fluorescence in situ hybridization (RNA FISH) and RT-qPCR experiments revealed that TBT enhanced the steady-state mRNA levels of two key genes for de novo lipogenesis, the transcription factor SREBF1 and its downstream enzymatic target, FASN. Importantly, pre-treatment of cells with 2-deoxy-D-glucose reduced TBT-mediated lipid accumulation, thereby suggesting a role for active glycolysis during the process of lipid accumulation. As other RXRA binding ligands can promote RXRA protein turnover via the 26S proteasome, TBT was tested for such an effect in the two liver cell lines. We found that TBT, in a time- and dose-dependent manner, significantly reduced steady-state RXRA levels in a proteasome-dependent manner. While TBT promotes both RXRA protein turnover and lipid accumulation, we found no correlation between these two events at the single cell level, thereby suggesting an additional mechanism may be involved in TBT promotion of lipid accumulation, such as glycolysis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.