The Dynamics of Human Body Weight Change

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Abstract
An imbalance between energy intake and energy expenditure will lead to a change in body weight (mass) and body composition (fat and lean masses). A quantitative understanding of the processes involved, which currently remains lacking, will be useful in determining the etiology and treatment of obesity and other conditions resulting from prolonged energy imbalance. Here, we show that a mathematical model of the macronutrient flux balances can capture the long-term dynamics of human weight change; all previous models are special cases of this model. We show that the generic dynamic behavior of body composition for a clamped diet can be divided into two classes. In the first class, the body composition and mass are determined uniquely. In the second class, the body composition can exist at an infinite number of possible states. Surprisingly, perturbations of dietary energy intake or energy expenditure can give identical responses in both model classes, and existing data are insufficient to distinguish between these two possibilities. Nevertheless, this distinction has important implications for the efficacy of clinical interventions that alter body composition and mass. Understanding the dynamics of human body weight change has important consequences for conditions such as obesity, starvation, and wasting syndromes. Changes of body weight are known to result from imbalances between the energy derived from food and the energy expended to maintain life and perform physical work. However, quantifying this relationship has proved difficult, in part because the body is composed of multiple components and weight change results from alterations of body composition (i.e., fat versus lean mass). Here, we show that mathematical modeling can provide a general description of how body weight will change over time by tracking the flux balances of the macronutrients fat, protein, and carbohydrates. For a fixed food intake rate and physical activity level, the body weight and composition will approach steady state. However, the steady state can correspond to a unique body weight or a continuum of body weights that are all consistent with the same food intake and energy expenditure rates. Interestingly, existing experimental data on human body weight dynamics cannot distinguish between these two possibilities. We propose experiments that could resolve this issue and use computer simulations to demonstrate how such experiments could be performed.
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