Metabolic and Neural Adaptations to Weight Loss, Plateau, and Regain

Background: \- Many people can lose weight by changing their diet or exercise. However, most people eventually regain the weight over time. This weight regain may be related to changes in metabolism as well as changes in the brain caused by weight loss. Researchers want to learn more about these changes. Objective: \- To see how weight loss and regain affects the body s metabolism and the brain of obese but healthy adults. Eligibility: \- Obese but healthy adults age 18-55 who plan to participate in a weight loss program at one of several participating clinics or resorts. Design: * Participants will first be screened at home through questionnaires and telephone interviews. * Participants will then be screened at the NIH with blood tests, medical history, physical exam, electrocardiograms, and questionnaires. They will have a mock magnetic resonance imaging (MRI) scan. * At visit 1, participants will stay at the NIH and will: * have MRI and PET brain scans. * have body composition scans and measurements. * give blood samples. * eat a special diet. * wear a physical activity monitor. * provide a urine sample and body weight daily. * drink a special type of water to measure calorie burn. * wear a clear plastic hood over their head while lying down, to collect exhaled air. * spend 24 hours in a room that measures oxygen and carbon dioxide. * complete questionnaires and computer tasks. * After visit 1, participants will give daily urine samples and weight and physical activity measurements from home. Then they will follow a lifestyle intervention for weight loss and give daily weight and activity measurements. * Visits 2, 3, and 4 occur 1-26 months after the start of the weight loss program. Participants will repeat procedures from visit 1. Visits 1-4 last 4 days each. * Researchers will track participants weight and physical activity for up to 26 months after visit 2.