This study, conducted at the NIH Clinical Research Unit at the Phoenix Indian Medical Center, will examine how the body's metabolism (energy expenditure) changes when people overeat and when they fast and how different diets (e.g., high-protein or high-fat) affect metabolism. The results may provide information about whether there are mechanisms that make some people more resistant than others to gaining weight when they eat more.

Non-smoking healthy subjects between 18 and 55 years of age who weigh no more than 350 pounds may be eligible for this study. Participants undergo the following procedures:

• Pregnancy test for women of childbearing age.
• Oral glucose tolerance test. For this test, an I.V. line (needle attached to a plastic tube) is inserted into a vein to allow several blood draws without repeated needle sticks. After the first blood sample is drawn, the subject drinks a cola-flavored sugar solution. Five additional blood samples are then drawn over 3 hours.
• Blood test for DNA (genetic) studies related to obesity, diabetes and related medical problems.
• DEXA scan. This test measures body fat. The subject lies on a table while a very small dose of X-rays is passed through the body.
• Respiratory chamber. This test measures how many calories the body burns a day and assesses energy balance between intake and expenditure. Subjects stay in a room with two windows, equipped with a sink, toilet, television and DVD player, desk, chair, telephone and bed for 24 hours. The test is repeated five times during the first 18-day admission and 3 times during the second 13-day admission. For the first two sessions, subjects are fed a diet equal to the amount of energy their body uses. For the next 6 stays they are fed double the amount of calories their body usually uses for 5 of the stays and fast (consume nothing but water and soda without caffeine or calories) during 1 stay. The overfeeding diets may be high or low in protein, normal in protein, or high in fat. Blood tests are done on the day of each respiratory chamber session and a 24-hour urine sample is collected for one day while in the chamber.
• Eating behavior questionnaires.
• Psychological performance tests.

Some participants are asked to volunteer to repeat two of the chamber studies to validate the measurements. The repeat session includes only the fasting and the overfeeding with normal protein content.

All participants are followed at 6 months with blood tests, a DEXA scan, and urine tests (including pregnancy test for women). At annual visits for years 1 through 7, participants have the 6-month tests plus an oral glucose tolerance test.