Gene Expression and Inflammation in Overweight Subjects

This study will look at gene expression (whether particular sets of genes are activated \["turned on"\] or deactivated \["turned off"\]) in overweight people as compared to non-overweight individuals. It will also investigate the potential role of inflammatory and protective substances that are produced naturally by the body within fat tissue. Findings from the study may lead to the development of ways to predict who will respond best to diet therapy. Healthy individuals between 25 and 45 years of age may be eligible for this study. Overweight subjects must have a BMI of 25 to 40, and non-overweight control subjects a BMI of 19 to 24.9. Candidates are screened with a medical history, physical examination, blood tests and electrocardiogram (EKG). They are instructed to record their dietary intake for a 3-day period and to collect their urine for a 24-hour interval. Participants have their food records reviewed a week after the screening visit. They are then scheduled for an overnight admission to the Clinical Center. Non-overweight subjects have one or two inpatient stays; overweight subjects have six inpatient stays plus frequent nutrition counseling sessions. During the 2-day hospital admissions, the following studies are performed:

• DEXA scan to determine the percentage of body fat tissue. The subject lies on a table for about 15 to 60 minutes while the body composition is measured with very low-dose x-rays.
• Single-slice CT scan to compare the amount of fat tissue under the skin with that in the abdomen. The subject lies on a table for about 5 to 10 minutes while the CT scanner measures body composition with very low-dose x-rays.
• Subcutaneous fat microdialysis to investigate how weight loss affects the activity of fat tissue. A small tube (catheter) is placed into the fat tissue under the skin of the abdomen after numbing the skin with a local anesthetic. Fluid samples are collected through the tube. The procedure lasts overnight. In five non-overweight controls, a small amount of a substance called leukotriene B4 is put into their fat tissue to help adjust the instruments used in the study.
• Air-displacement plethysmography to measure body composition. Subjects wear close-fitting clothing and enter a small capsule called a Bod-Pod. They breathe normally in the capsule while their body fat composition is studied.
• Blood tests. Blood samples are drawn to analyze thyroid hormones, lipids, glucose, electrolytes, clotting factors, kidney function, red cells and DNA.
• Euglycemic-hyperinsulinemic clamp to measure the effects of insulin in the body and to derive an index of insulin-sensitivity. Catheters are placed in a vein in an arm and in a vein in the hand on the other side of the body. Insulin and glucose are infused through the catheter in the arm, and blood samples are drawn from the catheter in the hand every 5 minutes to measure glucose levels. The test lasts about 2 hours.
• Subcutaneous fat biopsy to find out how weight loss affects fat tissue characteristics, gene regulation and the ability to store glucose. A small sample of fat tissue is obtained from the skin of the abdomen after numbing the area with an anesthetic.
• Nutrition counseling for overweight subjects. A nutritionist reviews the food record and designs a personalized diet for each participant.
• Weight loss intervention for overweight subjects. In addition to individual nutritional counseling, group sessions are provided every 2 weeks during the first 3 months of the study and then every month.