Cellular Dynamics of Subcutaneous Fat Distribution in Obese Women

Adipose tissue expandability and the distribution of stored fat in the body are stronger
predictors of health risk. A better understanding of the factors that determine regional fat
mass growth may lead to developing new strategies for prevention or treatment of metabolic
complications of obesity. The objective of this proposal is to study the responsiveness of
different fat depots to adipogenic stimulation in upper-body and lower-body obese women.

Inclusion Criteria:

- You are a pre-menopausal woman between 18-40 years of age

- Your Body Mass Index (BMI, weight-to-height2 ratio) is 27 - 38 kg/m2, inclusive

- The ratio of your waist-to-hip circumferences is either >0.84 ("apple"-type body
shape) or <0.77 ("pear"-type body shape)

- You are willing to undergo a drug intervention for 16 weeks

- You are willing to drink heavy water [similar to the ordinary water that is highly
enriched in the naturally occurring stable (non-radioactive) form of hydrogen,
deuterium; also called deuterium-labeled water] for 8 weeks before the beginning and
during the second half of the drug intervention; you will need 24-hours access to a
refrigerator for storage of the water.

- You agree to use a double barrier method as a form of birth control to prevent
pregnancy. Oral contraceptives (birth control pills) are not allowed in the study.
Acceptable methods of birth control are condoms, spermicide, IUD (intrauterine device,
must be hormone free - see list in clinic), diaphragm and abstinence. An example of a
double barrier method would be condoms plus spermicide, etc.

Exclusion Criteria:

- You have gained or lost more than 4.5 lb (2 kg) in the last 3 months

- You have had significant changes in the diet or level of physical activity within the
past month

- You have a blood sugar of greater than 100 or a diagnosis of diabetes.

- You have abnormal liver enzyme values from your blood work

- You have a history of heart, kidney, lung, liver, and thyroid disease

- You have an average blood pressure >140/90 at your screening visit

- Have you had a positive test for human immunodeficiency virus (HIV), hepatitis B or
hepatitis C?

- You require chronic use of medications including diuretics, steroids, thyroid
hormones, and adrenergic-stimulating agents (bronchodilators, nasal decongestants)