This is an R21 application intended to test the hypothesis that bisphenol A diglycidyl ether (BADGE) acts as an obesogen, in vivo through a pathway that is independent of PPAR3. Prenatal and early postnatal events such as maternal nutrition, drug, and chemical exposure are received, remembered, and then manifested in health consequences later in life. The obesity epidemic costs more than $147 billion annually in the US, primarily by increasing health care costs. Emerging evidence supports an important role for environmental factors in obesity. Among these is exposure to endocrine disrupting chemicals. Our preliminary results demonstrate that BADGE induces adipogenesis in both mouse and human multipotent mesenchymal stem cells (MSCs) through a pathway that appears not to involve a key adipogenic gene - the peroxisome proliferator activated receptor gamma (PPAR3). We wish to test the hypothesis that BADGE acts as an obesogen, in vivo.
Two specific aims are proposed to test this hypothesis: 1) Does BADGE exposure predispose mice to increased adipogenesis and obesity and if so, does it alter lineage allocation in the MSC compartment? 2) What molecular pathway does BADGE act through to influence adipogenesis and obesity? The proposed work will facilitate rapid progress in understanding whether the high volume chemical, BADGE, acts as an obesogen, in vivo, at environmentally relevant doses and will provide insights into how endocrine disrupting chemicals influence adipogenesis and obesity.
Obesity is a major public health problem. We propose to elucidate how maternal and early life programming of adipose tissue development is influenced by the endocrine disrupting chemical, bisphenol A diglycidyl ether (BADGE). The successful completion of this research will make important contributions to understanding the developmental programming of obesity, how obesogens affect this process, and what is the contribution of altered stem cell programming.
|Chamorro-GarcÃa, Raquel; Blumberg, Bruce (2014) Transgenerational effects of obesogens and the obesity epidemic. Curr Opin Pharmacol 19:153-8|
|Chamorro-GarcÃa, Raquel; Kirchner, SÃ©verine; Li, Xia et al. (2012) Bisphenol A diglycidyl ether induces adipogenic differentiation of multipotent stromal stem cells through a peroxisome proliferator-activated receptor gamma-independent mechanism. Environ Health Perspect 120:984-9|