Obesogens: a unifying theory for the global rise in obesity

Despite varied treatment, mitigation, and prevention efforts, the global prevalence and severity of obesity continue to worsen. Here we propose a combined model of obesity, a unifying paradigm that links four general models: the energy balance model (EBM), based on calories as the driver of weight gain; the carbohydrate-insulin model (CIM), based on insulin as a driver of energy storage; the oxidation-reduction model (REDOX), based on reactive oxygen species (ROS) as a driver of altered metabolic signaling; and the obesogens model (OBS), which proposes that environmental chemicals interfere with hormonal signaling leading to adiposity. We propose a combined OBS/REDOX model in which environmental chemicals (in air, food, food packaging, and household products) generate false autocrine and endocrine metabolic signals, including ROS, that subvert standard regulatory energy mechanisms, increase basal and stimulated insulin secretion, disrupt energy efficiency, and influence appetite and energy expenditure leading to weight gain. This combined model incorporates the data supporting the EBM and CIM models, thus creating one integrated model that covers significant aspects of all the mechanisms potentially contributing to the obesity pandemic. Importantly, the OBS/REDOX model provides a rationale and approach for future preventative efforts based on environmental chemical exposure reduction.