Effects of Leptin on Body Weight and Neuroendocrine Axes After Gastric Bypass

This is a pilot and feasibility study to examine a novel intervention using leptin in weight-reduced individuals who have undergone bariatric surgery but still remain obese. Leptin, a peptide hormone secreted from adipose tissue, is a regulator of food intake and energy expenditure. Administration of leptin resulted in profound weight reduction in the few reported cases of obese individuals with genetic leptin deficiency. However, most obese people have increased leptin levels. Such individuals are said to be in a "leptin-resistant" state, whereby administration of physiological concentrations of leptin are ineffective at producing significant weight reduction. Roux-en-Y gastric bypass surgery (RYGBP) is more effective than diet alone in producing long-term reduction of body weight. Yet even after surgery there is a plateau in weight loss though the individual may still be obese and have or be at risk for obesity related morbidities. The investigators have shown that plasma leptin levels are significantly lower in women after RYGBP compared with BMI-matched controls. This state of relative hypoleptinemia or leptin insufficiency suggests that post-RYGBP individuals may be in a "leptin-sensitive" state and, thus, would undergo further weight loss when administered doses of leptin that would not normally result in significant weight reduction. This study will examine the effects of leptin administered by self-injection twice per day on body weight and endocrine function. All individuals will received leptin and placebo and different times during the 34 week study period.