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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

Title: Thyroid receptor antagonism as a contributory mechanism for adipogenesis induced by environmental mixtures in 3T3-L1 cells.

Authors: Kassotis, Christopher D; Kollitz, Erin M; Hoffman, Kate; Sosa, Julie Ann; Stapleton, Heather M

Published In Sci Total Environ, (2019 May 20)

Abstract: We previously demonstrated that indoor house dust extracts could induce adipogenesis in pre-adipocytes, suggesting a potential role for indoor contaminant mixtures in metabolic health. Herein, we investigated the potential role of thyroid receptor beta (TRβ) antagonism in adipogenic effects (dust-induced triglyceride accumulation and pre-adipocyte proliferation) following exposure to environmental mixtures (indoor house dust extracts). Concentrations of specific flame retardants were measured in extracts, and metabolic health information was collected from residents (n = 137). 90% of dust extracts exhibited significant adipogenic activity, >60% via triglyceride accumulation, and >70% via pre-adipocyte proliferation. Triglyceride accumulation was positively correlated with concentrations of each of twelve flame retardants, despite most being independently inactive; this suggests a putative role for co-exposures or mixtures. We further reported a positive correlation between dust-induced triglyceride accumulation and serum thyroid stimulating hormone concentrations, negative correlations with serum free triiodothyronine and thyroxine concentrations, and a positive and significant association between dust-induced triglyceride accumulation and residents' body mass index (BMI). We hypothesized that inhibition of TR antagonism might counteract these effects, and both addition of a TR agonist and siRNA knock-down of TR resulted in decreased dust-induced triglyceride accumulation in a subset of samples, bolstering this as a contributory mechanism. These results highlight a contributory role of environmental TR antagonism as a putative factor in metabolic health, suggesting that further research should evaluate this mechanism and determine whether in vitro adipogenic activity could have utility as a biomarker for metabolic health in residents.

PubMed ID: 30802659 Exiting the NIEHS site

MeSH Terms: 3T3-L1 Cells; Adipocytes/drug effects*; Adipogenesis/drug effects; Adipogenesis/genetics*; Adult; Aged; Aged, 80 and over; Air Pollution, Indoor/adverse effects*; Air Pollution, Indoor/analysis; Animals; Dose-Response Relationship, Drug; Dust*; Female; Humans; Male; Mice; Middle Aged; Thyroid Hormone Receptors beta/antagonists & inhibitors*; Triglycerides/metabolism*

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