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To the Editor: The protein hormone leptin appears to act as an afferent signal from adipose tissue to the brain indicating the state of energy reserves.¹ Both serum and cerebrospinal fluid (CSF) leptin concentrations increase with body fat²; however, CSF concentrations are generally 2 orders of magnitude lower than serum concentrations. The transport of leptin across the blood-brain barrier appears to occur via a saturable system, as has been demonstrated in mice.³ This suggests a mechanism by which obese people can be "resistant" to their higher circulating levels of leptin² and suggests that exogenous administration of leptin to treat obesity might be ineffective.² Results of a double-blind clinical trial demonstrated that exogenous leptin (daily bolus subcutaneous injections of up to 0.3 mg/kg) has a biologic effect.⁴ We report here data from a separate cohort of this clinical trial indicating that recombinant leptin enters the CSF.

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Six obese but otherwise . . . [Full Text of this Article]

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