Antiobesity therapeutics targeting energy expenditure

Abstract

Obesity and its associated morbidities and mortalities result when the balance between energy intake and expenditure is biased towards the former. Despite the resurgence of research into therapeutic control of body weight and composition, the obesity epidemic continues to be experienced worldwide. To date, approved therapeutics have addressed energy intake by acting on central neural circuits that regulate feeding or on peripheral mechanisms to reduce nutrient absorption from the gut. These approaches have met with only moderate success, and recently with safety concerns, leaving an unmet medical need for effective and safe pharmacotherapy for obesity and a significant challenge for the pharmaceutical industry. The majority of human obesity is associated with elevated circulating levels of the adipocyte-derived hormone leptin, and a concomitant resistance to this important regulator of both energy intake and expenditure. This review focuses on three pathways implicated in leptin signalling that may have pharmaceutical promise for increasing energy expenditure, and relevant patent activity in the last two years is evaluated.

• β
• ₃
• adrenergic agonists
• endocannabinoids
• energy expenditure
• obesity
• protein tyrosine phosphatases
• thyromimetics
• uncoupling proteins