Friday, November 5, 2021

Adult and prenatal exposures to the pesticide DDT and its metabolite DDE have been associated with risk of obesity in subsequent generations of people, mice and rats in numerous studies.  Our research indicates that these obesogenic effects are caused by impaired metabolism. We have observed that prenatal exposure to DDT or DDE impairs body heat production in mice from their first week of life to 9 months of age. Indeed, metabolic reductions in thermogenesis, the production of body heat, are associated not just with DDT and DDE exposures, but also with numerous pharmaceuticals and genes that are known to cause obesity. Epigenome studies in both mice and humans with DDT and DDE exposures have revealed extensive changes in DNA methylation enriching the thermogenesis pathway, including changes in DNA methylation of upstream signaling and substrate regulation pathways. Defects in the thermogenic function but not the structure of mouse brown adipose tissue and cultured brown adipocytes have observed. Additionally, prenatal DDT reduces the innervation of mouse brown adipose tissue, and the upstream synaptic connectivity is reduced by either DDT or DDE exposure prenatally. This body of research evidence indicates that both DDT and DDE act as obesogens by targeting both brown adipose and the sympathetic nervous system to impair thermogenesis.