Endocrine Disrupting Chemicals and Metabolic Disruption
1:00 pm US Eastern Time
Dr. Chris Kassotis: Impacts of Chemical Mixtures Isolated from Household Dust on Metabolic Health
Dr. Raquel Chamorro-Garcia: Environmental exposures and mechanisms of transgenerational epigenetic inheritance
Dr. Chris Kassotis:
Kassotis CD, Kollitz EM, Ferguson PL, Stapleton HM. (2018). Nonionic Ethoxylated Surfactants Induce Adipogenesis in 3T3-L1 Cells. Toxicol Sci. 162(1):124-136. doi:10.1093/toxsci/kfx234
Kassotis CD, Kollitz EM, Hoffman K, Sosa JA, Stapleton HM. (2019). Thyroid receptor antagonism as a contributory mechanism for adipogenesis induced by environmental mixtures in 3T3-L1 cells. Sci Total Environ. 666:431-444. doi:10.1016/j.scitotenv.2019.02.273
Dr. Raquel Chamorro-Garcia:
Chamorro-Garcia R, Diaz-Castillo C, Shoucri BM, et al. (2017). Ancestral perinatal obesogen exposure results in a transgenerational thrifty phenotype in mice. Nat Commun. 8(1):2012. doi:10.1038/s41467-017-01944-z
Diaz-Castillo C, Chamorro-Garcia R, Shioda T, Blumberg B. (2019). Transgenerational Self-Reconstruction of Disrupted Chromatin Organization After Exposure To An Environmental Stressor in Mice. Sci Rep. 9(1):13057. doi:10.1038/s41598-019-49440-2
Obesity is a worldwide pandemic that also contributes to the increased incidence of other diseases such as type 2 diabetes. Increased obesity is generally ascribed to positive energy balance. However, recent findings suggest that exposure to certain endocrine-disrupting chemicals during critical windows of development may play an important role in the current obesity trends. Several experimental approaches, from in vitro cell cultures to transgenerational in vivo studies, are used to better understand their mechanisms of action. Our speakers, Dr. Kassotis and Dr. Raquel Chamorro-Garcia discussed the current state of the field and their contribution to it.
Dr. Kassotis spoke on the impacts of chemical mixtures isolated from household dust on metabolic health. Obesity and metabolic disorders are a large societal concern and generate significant human health care costs. Recently, attention has focused on the potential for environmental contaminants to act as metabolic disruptors through disruption of various nuclear hormone receptor pathways. His research has sought to evaluate the potential for diverse environmental contaminants to promote fat cell development, using an in vitro model of adipogenesis. He has reported that numerous indoor semi-volatile organic contaminants can promote fat cell development, and that mixtures of these chemicals present in house dust are sufficient to drive fat cell development at low, environmentally relevant levels. Moreover, he reported an association between the extent of house dust extract-induced fat cell development and the body mass index of people living in these homes. He also discussed some of their research evaluating underlying mechanisms, identifying causative chemicals, and next steps.
Dr. Chamorro-Garcia presented on environmental exposures and mechanisms of transgenerational epigenetic inheritance. A key challenge of the modern world relates to how our contribution to environmental degradation has a pervasive effect on our own health and the health of future generations. There is evidence from human epidemiological studies and animal models demonstrating that exposure to environmental agents prior to conception or during early development can increase disease susceptibility later in life and even transgenerationally in future generations. This seems to occur, at least partially, because of non-mutagenic alterations of the germline. Often, the exposure to environmental agents result in metabolic alterations such as obesity in the offspring of exposed individuals and even transgenerationally. Therefore, it is likely that the ramping rates of metabolic diseases worldwide have had a significant component that is associated with current and ancestral exposures to environmental agents. Nevertheless, the mechanisms through which exposure to these agents results in metabolic diseases in the offspring and future generations remain unclear.
Raquel Chamorro-Garcia, PhD, completed her PhD at the Universidad Autonoma of Madrid (Spain) and after that she came to the U.S. to do a post-doc in the laboratory of Prof. Bruce Blumberg at University of California Irvine. She started her position as Assistant Professor at the University of California Santa Cruz on July 1st, 2019.
The Chamorro-Garcia lab is interested in better understanding how environmental agents such as pollutants, diets, temperature or stress, shape our phenotype. Her main focus is to study mechanisms of genome-environment interactions using mouse models. Her work integrates epigenomic, transcriptomic, and physiological analyses to reveal how environmental stressors lead to the modulation of the expression of the genome. Her current emphasis is on alterations of chromatin organization during early embryonic development and how this disruption is propagated through development and across generations contributing to phenotypic variation and disease.
Chris Kassotis, PhD, is an incoming Assistant Professor (9/2020) in the Institute of Environmental Health Sciences and Department of Pharmacology at Wayne State University in Detroit. He is currently a K99 Postdoctoral Research Fellow in the Nicholas School of the Environment at Duke University. He completed his PhD at the University of Missouri working with Susan Nagel and Fred vom Saal to assess unconventional oil and gas operations as a novel source of endocrine disrupting chemicals, and the potential for adverse human and animal health outcomes from exposure. He is now working in Heather Stapleton's lab at Duke and Seth Kullman's lab at North Carolina State to assess the adipogenic/obesogenic activity of complex chemical mixtures (e.g. indoor house dust) via a combination of cell and zebrafish models.