Abstract
Obesity is an epidemic in the United States and worldwide. Although the personal, societal, and economic costs of this disorder are staggering, the medical research community has yet to develop definitive therapies. Progress has been made in understanding basic processes that underlie normal regulation of body adipose stores. However, mechanisms that account for the majority of human obesity have yet to be identified. Based upon current models of body weight regulation, the hypothesis is discussed herein that hypothalamic responses to “adiposity signals uo; such as insulin and leptin are disrupted in the setting of obesity. Recent work has determined specific mechanisms by which insulin and leptin normally act in the CNS and we will present mechanistic hypotheses for the development of resistance to these hormones. Furthermore, results of several macronutrient-based dietary intervention studies will be presented within the context of this model. Finally, we will discuss an emerging area that suggests that rewarding aspects per se of foods may contribute to the pathophysiology of obesity.
Keywords: obesity, diabetes, insulin, leptin, resistance, hypothalamus, signal transduction
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