ABSTRACT
EDCs are synthetic chemicals that were originally designed for a specic purpose such as a pesticide, plasticizer, or solvent. Such chemicals, when absorbed into the body, have the side effect of mimicking or blocking hormones by binding to their cognate receptors and disrupting the body’s normal functions.1 EDCs can also disrupt normal hormone levels by inhibiting or stimulating the production and metabolism of hormones or changing the way hormones travel through the body, thus affecting the functions that these hormones control. Some EDCs are obesogens that specically promote obesity by increasing the number of fat cells or the storage of fat into existing cells.3 They can also act on fat cells indirectly by altering metabolic rate and hormonal control of appetite and satiety.3 Nicotine, air pollution, polyhalogenated ame retardants, insecticides, fungicides, plastics, plasticizers, heavy metals, fructose, food additives, and some prescription
43.1 Introduction ..................................................................................................................................................................... 471 43.2 Endocrine Disrupting Chemicals and Obesogens ........................................................................................................... 471 43.3 Developmental Origins of Health and Disease ............................................................................................................... 472 43.4 General Mechanisms of Obesogen Exposure During Important Developmental Windows ........................................... 472 43.5 Examples of Obesogenic Chemicals in Animal and Human Studies ............................................................................. 473
43.5.1 Tributyltin and Triumizole: Obesogens that Act through PPARγ ..................................................................... 473 43.5.2 Obesogens with Unconrmed Mechanisms of Action ........................................................................................ 479
43.5.2.1 Bisphenol A ........................................................................................................................................... 479 43.5.2.2 Bisphenol A Diglycidyl Ether ............................................................................................................... 479 43.5.2.3 Organochlorines .................................................................................................................................... 480 43.5.2.4 Organobromine Flame Retardants ....................................................................................................... 480 43.5.2.5 Peruorochemicals ................................................................................................................................ 480 43.5.2.6 Phthalates .............................................................................................................................................. 480
43.6 Additional Mechanisms through which Obesogens Might Act ....................................................................................... 480 43.6.1 Obseogenic Chemical Inuences PPARγ in a Nonligand-Dependent Fashion ................................................... 480 43.6.2 Obesogenic Chemical Serves as a Ligand for a Different Receptor ................................................................... 481 43.6.3 Chemical Interferes with an Enzyme-Substrate Interaction ............................................................................... 481 43.6.4 Chemical Is a Nutrient Required for Development and Survival, but Has the Capacity to Be
Overconsumed and thus Adversely Affect Adipogenic Pathways, much as an EDC Does ................................ 481 43.7 Perfect Storm for Obesity ................................................................................................................................................ 481 Acknowledgments ..................................................................................................................................................................... 482 References ................................................................................................................................................................................. 482
medications have all been linked to obesity and/or the metabolic syndrome. This could be just the tip of the iceberg since there are close to 800 chemicals with reported EDC properties4 and only a very few of the ~80,000 chemicals in commerce have been tested for endocrine disrupting activity.
