Recombinant Leptin for Weight Loss in Obese and Lean Adults

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Abstract
The protein hormone leptin, encoded by the obese gene and produced by adipose tissue,1-6 appears to signal adiposity and modulate ingestive behavior. Several lines of evidence support this conclusion: exogenous leptin administration results in a loss of body fat in animals2,3,7,8; animals and humans who have a genetic deficiency of leptin exhibit extreme obesity1,5; and serum concentrations of leptin increase with body fat in very obese persons who do not have a genetic mutation.6,9-12 Leptin levels and body fat are highly correlated, and body fat accounts for approximately 50% to 60% of the variation in serum leptin concentrations among people.13 Other factors (eg, sex, diurnal variation, and serum insulin concentration) correlate to a lesser extent.13,14 Leptin concentrations in the cerebrospinal fluid (CSF) increase with body fat15-17 but are generally 2 orders of magnitude lower than serum concentrations. The ratio of CSF to serum leptin concentrations also appears to be lower in obese subjects.15,16 These relationships suggest that administering exogenous leptin might affect homeostatic mechanisms of energy regulation to alter body weight. Alternatively, the higher serum leptin concentrations in obese subjects may suggest that exogenous leptin administration would be ineffective in decreasing adiposity.15