We created the first validated 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 mathematical model of mouse energy metabolism and it provides a quantitative framework for investigating energy balance relationships in mouse models of obesity and diabetes.

Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2012
Total Cost
$119,716
Indirect Cost
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O'Neal, Timothy J; Friend, Danielle M; Guo, Juen et al. (2017) Increases in Physical Activity Result in Diminishing Increments in Daily Energy Expenditure in Mice. Curr Biol 27:423-430
Selimkhanov, J; Thompson, W C; Guo, J et al. (2017) A quantitative analysis of statistical power identifies obesity end points for improved in vivo preclinical study design. Int J Obes (Lond) 41:1306-1309
Friend, Danielle M; Devarakonda, Kavya; O'Neal, Timothy J et al. (2017) Basal Ganglia Dysfunction Contributes to Physical Inactivity in Obesity. Cell Metab 25:312-321
Bond, Nichole D; Guo, Juen; Hall, Kevin D et al. (2016) Modeling Energy Dynamics in Mice with Skeletal Muscle Hypertrophy Fed High Calorie Diets. Int J Biol Sci 12:617-30
Devarakonda, Kavya; Nguyen, Katrina P; Kravitz, Alexxai V (2015) ROBucket: A low cost operant chamber based on the Arduino microcontroller. Behav Res Methods :
Hall, Kevin D (2012) Metabolism of mice and men: mathematical modeling of body weight dynamics. Curr Opin Clin Nutr Metab Care 15:418-23
Guo, Juen; Hall, Kevin D (2011) Predicting changes of body weight, body fat, energy expenditure and metabolic fuel selection in C57BL/6 mice. PLoS One 6:e15961
Guo, Juen; Hall, Kevin D (2011) Challenges of indirect calorimetry in mice. Am J Physiol Regul Integr Comp Physiol 300:R780; author reply R781-2
Hall, Kevin D (2010) Mathematical modelling of energy expenditure during tissue deposition. Br J Nutr 104:4-7
Jo, Junghyo; Guo, Juen; Liu, Teresa et al. (2010) Hypertrophy-driven adipocyte death overwhelms recruitment under prolonged weight gain. Biophys J 99:3535-44

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