Predicting Changes of Body Weight, Body Fat, Energy Expenditure and Metabolic Fuel Selection in C57BL/6 Mice

The mouse is an important model organism for investigating the molecular mechanisms of body weight regulation, but a quantitative understanding of mouse energy metabolism remains lacking. Therefore, we created a mathematical model of mouse energy metabolism to predict dynamic changes of body weight, body fat, energy expenditure, and metabolic fuel selection. Based on the principle of energy balance, we constructed ordinary differential equations representing the dynamics of body fat mass (FM) and fat-free mass (FFM) as a function of dietary intake and energy expenditure (EE). The EE model included the cost of tissue deposition, physical activity, diet-induced thermogenesis, and the influence of FM and FFM on metabolic rate. The model was calibrated using previously published data and validated by comparing its predictions to measurements in five groups of male C57/BL6 mice (N = 30) provided ad libitum access to either chow or high fat diets for varying time periods. The mathematical model accurately predicted the observed body weight and FM changes. Physical activity was predicted to decrease immediately upon switching from the chow to the high fat diet and the model coefficients relating EE to FM and FFM agreed with previous independent estimates. Metabolic fuel selection was predicted to depend on a complex interplay between diet composition, the degree of energy imbalance, and body composition. This is the first validated mathematical model of mouse energy metabolism and it provides a quantitative framework for investigating energy balance relationships in mouse models of obesity and diabetes.