Central and peripheral molecular targets for antiobesity pharmacotherapy.

Obesity has emerged as one of the principal worldwide health concerns of the modern era, and there exists a tremendous unmet clinical need for safe and effective therapies to combat this global pandemic. The prevalence of obesity and its associated comorbidities, including cardiovascular and metabolic diseases, has focused the attention of those in drug discovery and development on generating effective modalities for the treatment and prevention of obesity. Early efforts in the field of obesity pharmacotherapy centered on the development of agents with indeterminate mechanisms of action. This led to treatment paradigms characterized by significant off-target effects. In the past two decades, new insights have been made into the physiologic regulation of energy balance and the subordinate central and peripheral circuits coordinating appetite, metabolism, and lipogenesis. These studies have revealed previously unrecognized molecular targets for controlling appetite and managing weight from which has emerged a new wave of targeted pharmacotherapies to prevent and control obesity.