Thyroid Receptor Antagonism as a Contributory Mechanism for Adipogenesis Induced by Environmental Mixtures in 3T3-L1 Cells

Sci Total Environ. 2019 May 20;666:431-444. doi: 10.1016/j.scitotenv.2019.02.273. Epub 2019 Feb 18.

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.

Keywords: Adipogenesis; Endocrine disrupting chemicals; House dust; Metabolic disruption; Obesity; Obesogen.

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*

Substances

  • Dust
  • Thyroid Hormone Receptors beta
  • Triglycerides