A Mathematical Model of Murine Metabolic Regulation by Leptin: Energy Balance and Defense of a Stable Body Weight

Abstract

We have developed a physiologically based mathematical model, with parameters derived from published experimental data, to simulate the regulatory effects of the leptin pathway on murine energy homeostasis. Model outcomes are consistent with data reported in the literature and reproduce key characteristics of the energy regulatory system, including compensatory responses that counteract changes in body weight and the failure of this ability when the leptin pathway is disrupted. Our model revealed the possibility of multiple steady states for body weight. It also provided a unified theoretical framework for two historically antagonistic hypotheses regarding body weight regulation (“set-point” versus “settling point”). Finally, our model has identified potential avenues for future investigations.