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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Kassotis, CD; Kollitz, EM; Hoffman, K; Sosa, JA; Stapleton, HM

Published Date

  • May 2019

Published In

Volume / Issue

  • 666 /

Start / End Page

  • 431 - 444

PubMed ID

  • 30802659

Pubmed Central ID

  • PMC6456385

Electronic International Standard Serial Number (EISSN)

  • 1879-1026

International Standard Serial Number (ISSN)

  • 0048-9697

Digital Object Identifier (DOI)

  • 10.1016/j.scitotenv.2019.02.273


  • eng