ENERGY HOMEOSTASIS IN HUMAN OBESITY

Columbia University Health Sciences, New York NY

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Abstract

Our previous studies have demonstrated that there is substantial metabolic opposition to the mainenance of an altered body weight. These studies examine body weight regulation from the perspective of four major processes which appear to be altered when body weight changes: 1) metabolic rate (rate of energy use), 2) activity of the nervous system regulating energy metabolism, 3) fat cell metabolism, 4) exercise (muscle) physiology. The basic design of this study is to observe these processes at usual weight and at various levels above and below these usual weights. A series of other measurements relevant to weight regulation will also be made. These include: a) vital signs (such as pulse, blood pressure, and temperature), b) ability to metabolize glucose, c) measurements of fat cell size and number, and d) determination of the chemical composition of muscle. This is a before/after study of the effects of weight loss within groups and a parallel study of effects of gender, somatotype, and ethnicity between groups. We will compare the changes in metabolic process which occur in obese and never-obese individuals following weight gain and/or weight loss to determine what differences there may be among obese, never-obese, and formerly-obese individuals. To accomplish these goals, formerly obese individuals must agree to be hospitalized for at least 2 weeks, never-obese individuals must agree to be hospitalized for at least 15 weeks and obese individuals must agree to be hospitalized for at least 6 months. Weight maintenance will be established by adjusting the number of calories that each subjects ingests per day as a liquid formula diet. Weight loss and gain will be accomplished by underfeeding (800 kcal/day of the formula) or overfeeding (solid food) respectively. Obese subjects will be studied at usual body weight, at 10% above usual weight, at 10% below usual weight and, if they wish, at 20% and 30% below usual weight. Never-obese subjects will be studied at usual weight, and at either 10% above or 10% below starting weight. Formerly obese subjects will be studied at usual weight and, in some instances, at 10% below that weight. At each weight plateau, every compartment or 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 and fat, in vivo studies of muscle efficiency by exercise and magnetic resonance imaging, indirect calorimetry (breathing in a ventilated hood), test of carbohydrate metabolism and nervous system tone which involve the placement of intravenous lines and administration of medication.