Feedback control of fat-free mass: a mechanism for the regulation of human body composition

We have developed a dynamic simulation model for change in human body mass and composition as a function of physical activity and nutrient intake. In constructing the model, we have hypothesized that set-point regulation of the fat-free mass (FFM) is central to determining body composition. In the set-point formalism, the FFM relaxes towards a set-point value when the system is not in steady state. Our expression for the FFM set-point takes account of activityinduced hypertrophy, derived from data on the steady-state relationship between FFM and total body mass. The FFM set-point also includes steady-state energy balance considerations. We have validated the model by comparison of simulation predictions to results obtained from short-term experimental studies on the time course of change in body mass and composition in response to overfeeding, fasting, and exercise. The model shows that FFM begins to change immediately with overfeeding or underfeeding, in agreement with experimental results. We have then extrapolated to predict long-term dynamics of body mass and composition in response to changes in nutrient intake and physical activity levels. The model suggests that physiological responses to step changes in nutrient intake and physical activity (where the nutrient and physical activity are held constant after the initial step change) may involve extremely long (several years) transients in body mass and composition, even when the model metabolic parameters do not change during that time. [D. Cotler has been supported by aGAANN fellowship.].