Toxicology Seminar Series: Michele La Merrill, PhD, Thursday, April 19

Please, join us on Thursday, April 19, 2018, for our second-to-last spring seminar, from 11:45 am – 1:00 pm in Field Auditorium, Environment Hall, on Duke University’s West Campus. Michele La Merrill, PhD, will be presenting a talk entitled “Mechanisms of impairments in brown adipose energy expenditure by obesogenic organochlorines.” Please see her talk abstract and bio below:

 Short bio

Michele A. La Merrill conducts integrated toxicological and epidemiological studies to understand susceptibility to the metabolic dysfunctions underlying obesity, diabetes, and breast cancer. Dr. La Merrill is an Assistant Professor of Environmental Toxicology and a member of the Environmental Health Center, Comprehensive Cancer Center, and Genome Center at the University of California, Davis. She teaches courses on the Biological Effects of Toxicants and Gene x Environment Interaction. She is also a faculty member of the Environmental Genomics and Systems Biology Division at the Lawrence Berkeley National Laboratory. Dr. La Merrill is a current recipient of a National Institute of Environmental Health Sciences Outstanding New Environmental Scientist award. She recently served on an International Agency for Research on Cancer Monograph that evaluated pesticides, including DDT and DDE, as potential carcinogens.

 Short abstract

The World Health Organization still recommends dichlorodiphenyltrichloroethane (DDT) for malaria control. Human migration, semi-volatility, persistence, and bioaccumulation continues to globalize exposures to DDT and its even more persistent metabolite dichlorodiphenyldichloroethylene (DDE) through the food supply. Further, most adults born in the U.S.A. prior to the DDT ban were highly exposed to DDT during the developmental window that programs lifetime metabolic function. Our meta-analysis indicates that developing humans exposed to elevated levels of DDE have an increased risk of obesity. We exposed pregnant and nursing mice to a low-dose technical mixture of DDT. Maternal DDT and DDE exposure increased the adiposity and insulin resistance of the adult mouse offspring. This long- term metabolic toxicity resulted from reduced energy expenditure due to underlying impaired brown adipose thermogenesis in mice. Indeed impaired thermogenesis was evident in mouse offspring on the last day of maternal dosing through nine months of age, when extensive transcripts involved in thermogenesis were down regulated in brown adipose. Differential DNA methylation analysis of brown adipose at the onset of impaired thermogenesis implicate reduced beta-adrenergic signaling in the exposure response. Further, respiration of cultured brown adipocytes decreased as a function of DDT or DDE sub-molar doses during adipogenic differentiation. These in vitro effects also coincided with decreased expression of protein and genes regulating thermogenesis, such as b3-AR and Ucp1. Our evidence suggests that the consistent association of DDE with human obesity may be explained by epigenetic- and adrenergic- impairment of brown adipose thermogenesis.


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