besity is a global epidemic that has proven daunting to prevent and treat. The prevalences of obesity (body mass index [BMI] Ͼ30) and morbid obesity (BMI Ͼ40) among American adults are about 30% and 5%, respectively. 1 Obesity is so strongly associated with medical comorbidities and mortality that it has begun to overtake infectious diseases as the most significant contributor to ill health worldwide. 2,3 Overweight persons are also frequently stigmatized and consequently suffer from low self-esteem. Their motivation to achieve and maintain weight loss is often Herculean. In 1 study of 47 patients who had durably lost 45 kg or more after bariatric surgery, 100% preferred to be deaf, dyslexic, diabetic, or have heart disease rather than be obese again; leg amputation and blindness were preferred by 91.5% and 89.4%, respectively. 4 The traditional treatment paradigm of diet, exercise, and medication generally achieves no more than a 5% to 10% reduction in body weight, 5,6 and recidivism after such weight loss exceeds 90% within 5 years. 7,8 This failure arises because a robust homeostatic system of body weight regulation compensates for weight loss with increased hunger and decreased energy expenditure. [9][10][11] The molecular mediators of these compensatory responses to weight loss are potential targets for antiobesity treatments. Ghrelin is a potent orexigenic (appetite-stimulating) peptide that seems to participate in the adaptive response to weight loss. Therefore, ghrelin holds promise as a target for both medical and surgical approaches to obesity.

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