Superfund Research Program
Environmental PPARγ Pathway Activators: Multifaceted Metabolic Disruptors Impacting Adipose and Bone Homeostatsis
Legacy Superfund chemicals (organotins, polychlorinated biphenyls (PCB)) and Superfund chemicals of emerging concern (organophosphate flame retardants, perfluoroalkyl substances) have been recognized as fat tissue and bone disruptors. Jennifer J. Schlezinger, Ph.D., and her research team investigated how these chemicals interact with signaling proteins, which change how fat, liver, and bone cells behave, on both the ecological and human-health levels. They showed that fish that were exposed long-term to PCBs in the environment have higher levels of body fat than those from a pristine environment. This difference likely results from differences in how the aryl hydrocarbon receptor (AHR) behaves. In contrast, tributyltin causes fin deformation in these fish without involvement of the AHR. A second set of signaling proteins that were studied are the peroxisome proliferator activated receptors (PPARs). These proteins regulate how our body uses (PPAR-alpha in the liver) or stores (PPAR-gamma in fat tissue) lipids. Researchers working on the Assessing the Relation of Chemical and Non-Chemical Stressors with Risk-Taking Behavior and Related Outcomes among Adolescents Living near the New Bedford Harbor Superfund Site Project, discovered that triphenyl phosphate, an organophosphate flame retardant, turns on PPAR-gamma in a particular way so that the fat cells that form are more likely to be undesirable white fat cells, which store lipid, rather than more healthy “brite” fat cells, which burn lipid. Brite fat cells are important in protecting us from metabolic diseases. The project investigators added a new class of chemicals to their repertoire this year, perflouroalkyl substances. They showed that perfluorooctanoic acid changes pathways in the liver that contribute to cholesterol homeostasis, potentially increasing the production of LDL (bad) cholesterol. The investigators continue to investigate how environmental chemicals change how these signaling proteins behave.