Background: Despite numerous studies on health hazards caused by Bisphenol A (BPA), consensus has not been reached as to its complex roles in various human diseases. This is partially due to a dearth of studies done under Good Laboratory Practices (GLP) using environmentally relevant BPA concentrations, and chronic exposure regimens from prenatal to adulthood. As BPA was originally thought to only disrupt estrogen signaling, most studies focused on its actions on the reproductive axis while overlooking its effects on metabolic homeostasis. This collaborative study represents a major attempt to rectify these deficiencies. Preliminary Data: Our laboratory was among the first to document both acute and chronic effects of BPA on the pituitary and reproductive organs of neonatal and adult male and female rats. More recently we reported that BPA at nM levels significantly inhibited the release of adiponectin, the major anti-diabetic adipokine, while stimulating the release of two inflammatory cytokines, TNFoc and IL-6, from adipose tissue explants. Over the last decade, our laboratory developed considerable expertise in studying many aspects of adipose tissue functions and the role of obesity in the metabolic syndrome in both rodents and humans. Objectives: The overall objective is to determine the effects of chronic BPA exposure on the development of the metabolic syndrome via alterations in selective adipose tissue functions. To this end, we will study the following parameters: 1) the regulation of adipokine, cytokine, receptor and lipogenic enzymes gene expression, 2) secretion of adipokines and cytokines, 3) changes in adipose tissue cellularity, and 4) the distribution of BPA between blood and adipose tissue.
This will be the first study which focuses on the metabolic effects of chronic low level exposure of BPA on events that contribute to the metabolic syndrome, a cluster of conditions which precedes diabetes and cardiovascular diseases. Unlike prior studies that examined gross effects of BPA on body mass, these studies will look at changes in discreet adipose depots and their cellular architecture. We expect to demonstrate a causal link between BPA exposure and the metabolic syndrome, thereby providing solid scientific data that can guide decision making by regulatory agencies.