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besity is a global epidemic that has proven daunting to prevent and treat. The preva- lences of obesity (body mass index (BMI)30) and morbid obesity (BMI40) among American adults are about 30% and 5%, respectively. 1 Obesity is so strongly associ- ated with medical comorbidities and mortality that it has begun to overtake infec- tious 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 gen- erally 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 en- ergy expenditure. 9-11 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.

Roles for Ghrelin in the Regulation of Appetite and Body Weight