Fat Metabolism and Melanocortin 3 Receptors in African Americans

• INCLUSION CRITERIA

Volunteers will qualify if they meet the following criteria

1. Age 18-55 years. Subject age is limited to 55y maximum because subjects are required to complete a maximal exercise test as part of their evaluations. Studying only younger patients decreases the risks of such exercise tests.
2. Non-Hispanic Black by self-identification with (to the best of the subject s knowledge) all 4 grandparents considered Non-Hispanic Black. Because T6K+V81I MC3R is 10-times more prevalent among Non-Hispanic Blacks, only Non-Hispanic Blacks will be eligible to participate.
3. Obesity, defined as body mass index (BMI) greater than or equal to 30 kg/m2 and weight under 450 lbs, in order for subjects to be able to undergo DXA scanning.
4. Willing to undergo genetic screening to establish that subject is either homozygous wild type for MC3R or homozygous for T6K+V81I MC3R, with the absence of other genetic causes of monogenic obesity (for both study and control groups).
5. Good general health. In general, subjects should take no medications. However, individuals taking medications for obesity-related co-morbid conditions, who have not had changes in dosage for more than 6 months, may be included, at the discretion of the principal investigator.
6. For females, a negative pregnancy test at the initial evaluation. Because pregnancy is a state in which weight gain is expected and appropriate, pregnant individuals would not be suitable for this study. Sexually active women must be using an effective form of birth control. These methods include abstinence, oral contraceptives, an intrauterine device (IUD), levonogestrol implants (Norplant), or medroxyprogesterone acetate injections (Depo-provera shots). If one of these cannot be used, contraceptive foam with a condom is recommended (One of these methods must have been used by the subject for at least two months prior to the start of the study).

EXCLUSION CRITERIA

Volunteers will be excluded (and referred to non-experimental treatment programs as needed) for the following reasons:

1. Subjects with a major medical illnesses that in the opinion of the medical team would impede interpretation of results, including significant renal, hepatic (other than obesity-related steatosis), gastrointestinal, most endocrinologic (e.g., Cushing syndrome, untreated hyper- or hypothyroidism, pheochromocytoma), hematological problems (e.g. -PT/PTT values that are prolonged greater than or equal to 3 seconds from the upper limit of the normal or thrombocytopenia < 70,000) or pulmonary disorders; or porphyria;
2. Current users of tobacco products;
3. Subjects following a diet with specific food requirements such as vegetarian, vegan, or kosher;
4. Women who are pregnant or who are currently nursing an infant or have irregular menses;
5. Individuals who have current substance abuse or a psychiatric disorder or other condition that in the opinion of the investigators would impede competence or adherence;
6. Recent (3 months) use of anorexiant medications;
7. Subjects using medications known to affect glucose and fatty acid metabolism and/or absorption;
8. Subjects on anticoagulatns, or those who cannot safely stop NSAIDs or antiplataelet agents for 10 days (a week prior to and three days after their biopsy)
9. Subjects with weight change of more than 3% of body weight in the past two months;
10. Subjects currently using a weight loss diet;
11. Subjects with untreated hypertension: a consistently (2 weeks apart) elevated systolic blood pressure of greater than 160 mm Hg and/or a diastolic flood pressure greater than 95 mm Hg.
12. Subjects with a history of keloid formation, since such individuals may have greater scarring after biopsies or intravenous catheter placement.