Pharmacokinetics of Leptin Administration During Fasting

Leptin is a newly-identified hormone secreted by fat cells under normal conditions that acts
in the brain to decrease appetite and increase long term energy usage. Leptin levels usually
go down when people are not eating for extended periods of time. Changes in metabolism and
certain hormone levels also occur with fasting. By studying the pharmacokinetics of leptin
administration, we can evaluate the changes of leptin levels in response to giving different
doses of leptin as well as acute changes of other hormones in response to leptin levels.
Investigations such as this one have important implications for the future therapeutic use of
leptin, including determining the appropriate dose of leptin to use in future studies
involving leptin administration.

Comparison: subjects receiving leptin at 3 different doses in the fed state compared to the
fasting state

Inclusion Criteria:

- healthy men with body mass indices (BMI) <25 kg/m2)

- overweight otherwise healthy men with BMI > 27 kg/m2

- healthy lean women with BMI<25 kg/m2

- overweight otherwise healthy women with BMI > 27 kg/m2

Exclusion Criteria:

- history of any illness that may affect the concentrations of the hormones that will be
studied (such as anemia, infectious diseases, renal or hepatic failure, diabetes
mellitus, cancer, lymphoma, hypogonadism, malabsorption or malnourishment, hypo or
hyperthyroidism, hypercortisolism, alcoholism or drug abuse, eating disorders)

- on medications known to affect the hormones to be measured in this study (such as
glucocorticoids, anti-seizure medications or thyroid hormones)

- known history of anaphylaxis or anaphylactoid-like reactions or who have a known
hypersensitivity to E. Coli derived proteins

- women who are breast feeding, pregnant, or wanting to become pregnant during the next
6 months