Our previous studies have demonstrated that there is substantial metabolic opposition to the maintenance of an altered body weight. These studies examine body weight regulation from the perspective of exercise physiology, which appears to be altered when body weight changes. The basic design of this study is to observe these processes at usual weight and below these usual weights. This is a before/after study of the effects of weight loss within groups and a parallel study of effects of gender between groups. We will compare the changes in metabolic processes which occur in obese individuals following weight loss to determine what differences there may be among obese, never-obese, and formerly-obese individuals. All subjects will undergo graded exercise testing, NMR spectroscopy studies, body composition analysis, either while in-patients at the CRC at Columbia Presbyterian Medical Center or as out-patients. Subjects who elect to participate fully in these studies will be admitted overnight to the CRC at Columbia Presbyterian Medical Center. On the day of admission, they will undergo graded exercise testing. The following morning they will undergo measurement of resting metabolic rate before arising from bed and then undergo a biopsy of the vastus lateralis muscle. Subjects will then be discharged. All will initially be stable at their usual body weight, defined as weight stable within 5 kg for at least 6 months, as determined by their referring physician. Following completion of the studies outlined above and below, subjects will undergo supervised weight reduction as out-patients with their referring physician. Once weight reduction loss is completed to a point deemed acceptable to both the patient and their referring physician, and the subject has been weight stable within 5 kg for at least 2 months, the patients will be readmitted and the studies repeated. At each weight plateau, in vivo, and in some cases in vitro, skeletal muscle physiololgy, body composition, and, in some subjects, resting metabolic rate, every compartment of energy expenditure (resting energy expenditure, work of digestion, efficiency of muscle) will be examined in great detail. These examinations will include needle biopsies of muscle, in vivo studies of muscle efficiency by exercise and magnetic resonance imaging, indirect calorimetry (breathing in a ventilated hood), and measurement of body composition by underwater weighing and dual photon beam absorptiometry.
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