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The role of energy expenditure in energy regulation remains a subject of continuing controversy. New data have emerged from studies conducted over the last decade demonstrating that energy expenditure is a critical factor contributing to successful energy regulation in normal individuals, as well as to the disregulation of energy balance that characterizes obesity. Reduced energy expenditure appears to facilitate weight gain in individuals susceptible to obesity and also appears to reduce the extent of body energy loss during undereating in both lean and obese individuals. The magnitude of the reduction in energy expenditure during, and perhaps after, weight loss is greater than expected on the basis of the reduction in body weight and appears to occur in response to undefined underlying determinants of energy regulation. In addition, exercise intervention studies and cross-sectional investigations of the relationship between energy expenditure for physical activity and body composition demonstrate an apparent equilibration between physical activity and body fat content. This equilibration is suggestive of a direct influence of physical activity on the underlying metabolic determinants of energy balance.