Obesity: Increasing Awareness of Novel Environmental Factors

Over the past 20 years, the molecular underpinnings of energy homeostasis have come to light (1–4) at a rate strikingly similar to that of the rising prevalence of obesity (5,6). The fact that one is statistically more likely to be overweight or obese in the U.S. today has profound ramifications for basic scientific research, translational research, public policy, and our health care economy. ### Homeostatic regulation of feeding. Current obesity statistics generate a striking contrast to abundant experimental evidence indicating that body adiposity is (or can be) a remarkably tightly regulated physiological variable (7–9), much like blood glucose concentration. Studies in rodent models, many of which have been confirmed in humans, have identified a plethora of humoral signals, neuropeptides, brain nuclei, and metabolic pathways involved in the precise physiological mechanism termed energy homeostasis (10). Primitive brain structures involved, such as the hypothalamus and hindbrain, are capable of sensing the status of body energy stores and initiating the appropriate homeostatic responses to maintain optimal body adiposity. Unfortunately, this rapidly expanding body of basic science in energy homeostasis has yet to be translated into efficacious therapies or prevention strategies for human obesity. Similarly, the limited translational research experience in obesity, which has focused on increasing physical activity, changing patterns of dietary practices, and modifying the built environment in communities, has yet to …