The effects of leptin administration in non-obese human subjects

Objective: Body fatness is partly under hypothalamic control with effector limbs that include the endocrine system and the autonomic nervous system (A NS). In previous studies of both obese and never-obese subjects, we have sh own that weight increase leads to increased sympathetic and decreased paras ympathetic activity, whereas weight decrease leads to decreased sympathetic and increased parasympathetic activity. We now report on the effect of lep tin, independent of weight change, on the ANS. Research Methods and Procedures: Normal weight males (ages 20-40 years) wer e fed a solid food diet, measured carefully to maintain body weight, for 3 weeks, as inpatients at the Rockefeller University General Clinical Researc h Center. In a single-blind, 22-day, placebo/drug/placebo design six subjec ts received leptin 0.3 mg/kilogram subcutaneously for 6 days. ANS measures of amount of parasympathetic control and sympathetic control of heart perio d (interbeat interval) were made by sequential pharmacological blockade wit h intravenous atropine and esmolol. Norepinephrine, dopamine, and epinephri ne levels in 24-hour urine collections were also measured as well as restin g metabolic rate. Results: Sufficient food intake maintained constant body weight in all subj ects. There was no evidence that leptin administration led to changes in en ergy metabolism sufficient to require additional food intake or to alter re sting metabolic rate. Likewise, leptin administration did not alter autonom ic activity. Parasympathetic control and sympathetic control, as well as th e urinary catecholamines, were not significantly affected by leptin adminis tration. Glucose and insulin levels were increased by food intake as expect ed, but leptin had no affect on these levels before or after food intake. Discussion: ANS responses to changes in energy metabolism found when food i ntake and body weight are altered were not found in these never-obese subje cts given leptin for 6 days. Although exogenous leptin administration has p rofound effects on food intake and energy metabolism in animals genetically deprived of leptin, we found it to have no demonstrable effect on energy m etabolism in never-obese humans. The effects of longer periods of administr ation to obese individuals and to those who have lost weight demand additio nal investigation.