Organostannic compounds as PPAR gamma agonists

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 366-382-Physiological Impacts of Endocrine Disrupting Chemicals
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-371
Isabella Gontijo de Sá Leao1, Angelica Amorim Amato2, Natacha Thalita Santos Amorim1, Leticia Mendes Cortes3 and Francisco de Assis Rocha Neves*4
1University of Brasilia, Brazil, 2University of Brasilia, Brasília, Brazil, 3University of Brasilia, 4University of Brasilia, Brasilia, DF, Brazil
The parallel increase in the amount of environmental contaminants and in the prevalence of certain human diseases has led to a growing interest in understanding how these compounds, referred to as endocrine disruptors, may affect human health. In this scenario, the obesity epidemics worldwide may be viewed not only as the result of the interplay between genetic and lifestyle factors but also of the exposure to environmental contaminants that might alter metabolic homeostasis. Organostannics are a distinct class of organic pollutants related to paints used in overseas transports and agrotoxics, and have emerged as potential metabolic disruptors due to their effects on nuclear receptors. Tributyltin (TBT) was the first organostannic compound studied and has been shown to be a strong agonist for peroxisome proliferator-activated receptor-g (PPARg) and stimulate adipogenesis, with the potential to induce weight gain and other unfavorable effects of strong PPARg activation. However, little is known about the effect of other organostannic compounds on this receptor. In this study, we describe the agonist effects of the organostannic pollutants dibutyltin dilaurate (DBT) and benzoate TBT on PPARg in HeLA and human mesangial cells cotransfected with PPARg-GAL4 and the UAS-tk-luc reporter. This effect appeared to be specific for PPARg, since DBT, benzoate TBT and also TBT had no activity on glucocorticoid, estrogen and thyroid hormone receptors when assessed by reporter gene assays using the respective expression vectors and responsive element-driven luciferase reporter. Further studies are being carried out to investigate the effect of these compounds on cell-based adipogenesis, PPARg-responsive genes and also in vivo. Additionally, we seek to investigate their mode of binding to the binding pocket of PPARg. These results may provide a better understanding of how these pollutants affect in human health and possibly the increasing rates of obesity and its associated diseases worldwide.

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