MedicalResearch.com Interview with:
Christopher D. Kassotis, Ph.D.
NRSA Postdoctoral Research Scholar
Nicholas School of the Environment
Durham, NC 27708
MedicalResearch.com: What is the background for this study? What are the main findings?
- So this was something that Heather Stapleton had been curious about for years, as she’s been one of several researchers characterizing the hundreds of chemicals that have been measured in indoor house dust. Before I came to Duke, one of her PhD students had measured the ability of many common indoor contaminants to activate the peroxisome proliferator activated receptor gamma (PPARg). The majority of these chemicals did, often quite well, which led to them testing indoor house dust extracts, also finding that the majority of dust extracts were also able to do so at very low levels. As PPARg is often considered the master regulator of fat cell development, the next obvious question was whether these common contaminants (and house dust) could promote fat cell development in cell models. My first work at Duke evaluated a suite of common indoor contaminants, finding that many of these chemicals could promote fat cell development, and that low levels of house dust extracts did as well.
- We next explored this more systematically in a group of adults involved in a thyroid cancer cohort (this was just recently published in Science of the Total Environment:
- In this study we evaluated the extent to which house dust extracts could promote fat cell development in a common cell model, and associated this with the metabolic health of adults living in these homes. We found that the greater extent of fat cell development was associated with significantly greater thyroid stimulating hormone concentrations (control residents only, with no evidence of thyroid dysfunction) and lower free triiodothyronine (T3) and thyroxine (T4). We further found a significant and positive association between extent of fat cell development and the body mass index (BMI) of all adults in the study. So this suggested that the indoor environment might play a role in the BMI and metabolic health of residents, and we next wondered if this would be more pronounced in children, who may be exposed to these contaminants during a critical window of development.
- The next step, for our current work, was to substantiate these effects in a larger group of households, each with children.
- Our major conclusions thus far have been that ~80% of house dust extracts promote significant fat cell development in a cell model – either via development from precursor cells into mature fat cells, measured via accumulation of lipids into the cells, or via the proliferation of those precursor fat cells. We also reported positive correlations of fat cell development with the concentrations of 70 different contaminants in the dust from these homes, suggesting that mixtures of contaminants are likely all acting weakly to produce these effects in combination. We’ve also begun to assess the other chemicals present in dust – chemistry can be either targeted (measuring concentrations of specific known chemicals in a sample), or non-targeted, where you try and determine the identity of the other chemicals in a sample. This has greater utility for identifying many more chemicals, though you will often not get chemical concentrations from this, nor absolute confirmed identification – just varying degrees of certainty based on evidence.
Thus far we report approximately 35,000 chemicals in house dust samples across this study, and differential analyses have begun to pick out the few (less than 10 in each case) chemicals most differentially expressed between samples that exhibit high degrees of fat cell development in the lab vs inactive samples, for example, or which are differentially present in the homes of children categorized as obese or overweight. We are now working to confirm identity of these select contaminants that are more likely to be causative factors in the results we have observed.
MedicalResearch.com: What should readers take away from your report?
Response: Based on our previous study, there seems to be an association between the extent of dust-induced fat cell development in the lab and the metabolic health of people living in those homes. This is not necessarily causative – it could be that people classified as obese or overweight have different purchasing practices and as such different chemicals present in the dust of their homes. Further work needs to evaluate this relationship and replicate it in other studies.
We do know that small concentrations of dust from peoples main living areas is sufficient to promote the development and proliferation of fat cells in the lab, and that disruption of the thyroid receptor seems to be at least a contributory mechanism for those effects.
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
- So ultimately we did not, on further analysis, reveal any striking impacts on child metabolic health. We saw quite significant impacts on adult health previously, and hypothesized that we might see more significant impacts in children, due to the above.
Herein, we split the “active” dust extracts (those able to drive fat cell development in our cell model) into equal groups (tertiles). Our results suggest that greater adipogenic activity may be associated with greater age-adjusted growth rates (BMI Z scores and weight for height Z scores (account for the expected range at the child’s current age) in children living in these homes. These effects were only significant in the highest tertile of adipogenic activity and with wide confidence intervals, so this was not a strong effect. One potential factor in this weaker association than we observed in adults is that in our previous study, the adults had lived in their homes for an average of 9 years, meaning that their dust was a good marker for long-term exposure to contaminants. This was not as much the case in TESIE, as many of our families moved early in life, many living in their current home for <2 years. This may have contributed to the weaker associations we observed here, and should be further investigated/substantiated in future studies.
- We also continue to assess mechanism – I am still working to assess two potential causative pathways (activation of PPARg) and inhibition of thyroid receptor beta (TRb). In our previous study in adults, we demonstrated that TRb was a contributory pathway leading to at least some of the adverse effects observed therein. In our current work, our analysis thus far finds no relationship between activation of PPARg and fat cell development by dust, though again a strong relationship between thyroid receptor disruption and activity.
- Another path we are still evaluating is mixture effects of contaminants and identifying causative chemicals. We have measured 111 contaminants in these dust samples, but we suspect that mixture effects or as of yet undetermined chemicals are promoting most of the adipogenic activity herein. We have begun to assess that through non-target analysis, identifying chemicals present in the samples that are associated with the adipogenic activity and identifying them.
MedicalResearch.com: Is there anything else you would like to add?
- Our previous study demonstrated that indoor contaminants are associated with the metabolic health (thyroid hormone levels and BMI) of adult residents. Our results suggest that greater adipogenic activity may be associated with greater age-adjusted growth rates in children living in these homes as well, but this was less significant than what we previous demonstrated in adults. I hope this increases attention on exposures in the indoor environment – we are often more concerned with external exposures, or via our diet, and our research increases our understanding of the indoor environment as an important exposure source that could contribute to certain chronic adverse health effects.
- The indoor environment contains a vast assortment of chemicals. The research we are doing via non-target analysis has found approximately 35,000 chemicals in the house dust of these homes. I hope this raises awareness of the vast number of chemicals in the indoor environment. There are numerous options for reducing these chemicals, from flame retardants to pesticides to plasticizers, etc., and I hope it will allow for more informed decisions from consumers when they make future purchasing decisions.
We have no disclosures to report.
ENDO 2019 abstract:
Non-Target Assessment of Contributory Chemicals and In Vitro Assessment of Molecular Mechanisms of Indoor House Dust Extract-Induced Adipogenesis in 3T3-L1 Cells
Christopher Kassotis, PhD, Kate Hoffman, PhD, P. Lee Ferguson, PhD, Heather Stapleton, PhD.
Duke University, Durham, NC
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