Author Interviews, Duke, Endocrinology, Environmental Risks, Thyroid Disease, Weight Research / 27.03.2019
Chemicals in Household Dust May Promote Fat-Cell Development
MedicalResearch.com Interview with:
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Dr. Kassotis[/caption]
Christopher D. Kassotis, Ph.D.
NRSA Postdoctoral Research Scholar
Stapleton Lab
Duke University
Nicholas School of the Environment
Durham, NC 27708
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Kassotis[/caption]
Christopher D. Kassotis, Ph.D.
NRSA Postdoctoral Research Scholar
Stapleton Lab
Duke University
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: https://www.sciencedirect.com/science/article/pii/S0048969719307715?dgcid=author
- 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.


Dr. Gyamfi-Bannerman[/caption]
Cynthia Gyamfi-Bannerman, MD, MSc
Ellen Jacobson Levine and Eugene Jacobson
Professor of Women's Health in Obstetrics and Gynecology
Director, Maternal-Fetal Medicine Fellowship Program
Co-Director, CUMC Preterm Birth Prevention Center
Columbia University
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: In 2016 our group published the findings of the Antenatal Late Preterm Steroids (ALPS) trial in the NEJM. We found that administration of antenatal corticosteroids to women at high risk for delivery from 34-36 weeks decreased breathing problems in their neonates. This treatment had been traditionally only given at less than 34 weeks.
The current paper is a cost analysis of that trial. We found that the treatment was also cost effective. From a cost perspective treatment was both low cost and highly effective (the options are low cost, low effect/low cost/high effect, high cost/low effect, high cost/high effect).
Dr. Rhee[/caption]
Chanu Rhee, MD,MPH
Assistant Professor of Population Medicine
Harvard Medical School / Harvard Pilgrim Health Care Institute
Assistant Hospital Epidemiologist
Brigham and Women’s Hospital
MedicalResearch.com: What is the background for this study?
Response: Sepsis is the body’s reaction to a serious infection that results a cascade of inflammation in the body and organ dysfunction, such as low blood pressure, confusion, or failure of the lungs, kidneys, or liver. Sepsis is a major cause of death, disability, and cost in the U.S. and around the world. Growing recognition of this problem has led to numerous sepsis performance improvement initiatives in hospitals around the country. Some of these efforts have also been catalyzed by high-profile tragic cases of missed sepsis leading to death, which may have contributed to a perception that most sepsis deaths are preventable if doctors and hospitals were only better at recognizing it.
However, the extent to which sepsis-related deaths might be preventable with better hospital-based care is unknown. In my own experience as a critical care physician, a lot of sepsis patients we treat are extremely sick and even when they receive timely and optimal medical care, many do not survive. This led myself and my colleagues to conduct this study to better understand what types of patients are dying from sepsis and how preventable these deaths might be.
Dr. McCrory[/caption]
Megan A McCrory, PhD, FTOS
Research Associate Professor
Dept of Health Sciences
Sargent College of Health and Rehabilitation Sciences
Boston University 02215
MedicalResearch.com: What is the background for this study?
Response: The prevalence of overweight and obesity has increased in the US, along with documented increases in portion size in the food supply. Fast food is popular, making up about 11% of adult daily calorie intake in the US, and over 1/3 of U.S. adults eat at fast food establishments on any given day. We therefore sought to examine changes in portion size, calories, and selected nutrients in fast-food entree, side, and dessert menu items across the years 1986, 1991, and 2016.
Dr. Mikkola[/caption]
Tomi Mikkola MD
Associate Professor
Helsinki University Hospital
Department of Obstetrics and Gynecology
Helsinki, Finland
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: In Finland we have perhaps the most comprehensive and reliable medical registers in the world. Thus, with my research group I have conducted various large studies evaluating association of postmenopausal hormone therapy use and various major diseases (see e.g. the references in the B;MJ paper). There has been various smaller studies indicating that hormone therapy might be protective for all kinds of dementias, also Alzheimer’s disease.
However, we have quite recently shown that hormone therapy seems to lower the mortality risk of vascular dementia but not Alzheimer’s disease (Mikkola TS et al. J Clin Endocrinol Metab 2017;102:870-7). Now in this upcoming BMJ-paper we report in a very large case-control study (83 688 women with Alzheimer’s disease and same number of control women without the disease) that systemic hormone therapy was associated with a 9-17% increased risk of Alzheimer’s disease.
Furthermore, this risk increase is particularly in women using hormone therapy long, for more than 10 years. This was somewhat surprising finding, but it underlines the fact that mechanisms behind Alzheimer’s disease are likely quite different than in vascular dementia, where the risk factors are similar as in cardiovascular disease. We have also shown how hormone therapy protects against cardiovascular disease, particularly in women who initiate hormone therapy soon after menopause.

Dr. Immler[/caption]
Dr Simone Immler PhD
School of Biological Sciences
University of East Anglia
MedicalResearch.com: What is the background for this study?
Response: Sperm produced by one male vary substantially both in their genetic content as well as their swimming ability including speed and duration. In a previous study in the zebrafish, we showed that sperm swimming duration is at least partly determined by the underlying haploid genetic content carried by the different sperm within an ejaculate (alavioon et al. 2017 PNAS). If sperm with different swimming ability differ in their genetic content, we expect to see differences among the offspring sired by sperm that vary on their swimming ability.
In our new study, we tested how selection on sperm swimming duration affects offspring fitness. We performed in vitro fertilisation assays mimicking natural conditions in the externally fertilising zebrafish. We split the ejaculate of one male into two halves and in one half we added the sperm straight away to the eggs, allowing all motile sperm to have a go at fertilising an egg. In the second half, we activated the sperm but delayed the moment of fertilisation by 25 seconds and thus selected for the longer swimming sperm. In this treatment only sperm that were still swimming after this period of time (about 50%) were able to fertilise an egg.
We then reared the offspring to adulthood and measured number of offspring produced throughout life and measured lifespan. We found that sperm that were able to swim for longer sired offspring that not only produced more and healthier offspring but also lived for longer than their full siblings sired by sperm with reduced swimming ability. Our previous research (Alavioon et al. 2017 PNAS) suggests that these differences are caused at least partly by genetic differences among sperm.