In Vivo Leptin Signaling in Humans After Acute Leptin Administration

Screening Visit During this visit, you will have a complete medical history taken and have a
physical examination performed by one of the study physicians. You will also have your height
and weight measured. You will have a blood drawn (approximately 2 tablespoons)and will have
an electrocardiogram (EKG). At the screening visit you will also meet with a dietician who
will review your food preferences with you in order to design the meals that you will receive
as part of the study.

Study Day #1: You will pick up your meals designed with the dietician. You will be provided
with meals for 48 hours prior to your fat biopsy. These meals will be designed by the
dietician based upon what you like to eat. You will also have your Resting Metabolic Rate
Measured.

Study Day #2: A nurse will will insert two intravenous catheters (IV) into a medium size vein
in each of your forearms. You will then have two fat and muscle thigh biopsy. One before and
one after leptin is given. You will stay in the hospital for three hours of observation.
During this time you will have your Resting Metabolic Rate measured and then you will be
provided with a meal.

Study Day #3: Seven to ten days after the biopsy, you will be asked to return to the hospital
so that the surgeon can inspect the wound.

Your participation in this study will involve 3 study visits, which will be spread out over
3-4 weeks.

Inclusion Criteria:

- For this pilot study we propose to enroll men and women, ages 18-65 years, with body
mass index (BMI) ranges meeting lean and obese criteria, and less than or equal to 45
kg/m2. Obese diabetics will also be included.

Exclusion Criteria:

- We will exclude subjects who require special diet prior to biopsy. We will exclude
subjects with a history of any illness, other than obesity and diabetes. Subjects
taking any medications that are known to influence glucose metabolism such as
glucocorticoids will also be excluded. Subjects who have a known history of
anaphylaxis or anaphylactoid-like reactions or who have a known hypersensitivity to E.
coli-derived proteins or anesthetic agents such as Lidocaine or Novocaine will be
excluded from the study. Women who are breast feeding, pregnant, or wanting to become
pregnant during the month following the study may not participate in this study. Women
participating in this study must use a contraceptive method to prevent pregnancy
(birth control pills, hormonal implants, intrauterine device (IUD), diaphragm with
intravaginal spermicide, cervical cap, male or female condom). If a woman suspects
that she has become pregnant during the study or within one month of completing study,
or if she does not use one of the contraceptive methods recommended by the
investigator, she will be instructed to notify the study staff immediately. Subjects
with a history of bleeding dyscrasia, poor wound healing or any medical condition
precluding supine position will be excluded from the study.