Pilot Study to Identify Environmental Obesogens (Chemicals That Cause Overeating) Using BRET (Bioluminescence Resonance Energy Transfer) and Cell-based Assays

The prevalence of obesity has been dramatically increasing worldwide during the last several decades. Because obesity is closely associated with chronic diseases, such as type 2 diabetes and cardiovascular diseases, the increase in obesity corresponds to a rise in mortality rates. There is growing epidemiological evidence indicating a positive correlation between the exposure of human population to endocrine-disrupting chemicals (EDCs, chemicals that affect hormone systems) and body weight, suggesting a possible role of EDCs in increasing obesity rates. The “obesogen hypothesis” proposes that exposure to a subset of these chemicals (obesogens) disrupts the body’s weight-control mechanisms and ultimately increases obesity. Leptin is an adipocyte-derived hormone that plays a key role in food intake and inhibits appetite by decreasing the activity of the orexigenic NPY/AgRP/GABA neurons and increasing the activity of the anorexigenic POMC/CART neurons in the hypothalamus. Leptin action is exerted through its binding to the leptin receptor (OB-R) expressed on the surface of these neurons. This pilot study aims to conduct a screening program against a chemical library of representative environmental compounds (using biophysical and cellbased assays) to identify environmental chemicals that act as leptin antagonists that may potentially trigger the onset of diet-induced obesity (DIO) in humans.