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Mathematical Modeling of Metabolism and Obesity

Mathematical Modeling of Metabolism and Obesity. Kevin D Hall Laboratory of Biological Modeling NIDDK March 6, 2009. “Systems Modeling” of Obesity. http://kim.foresight.gov.uk/Obesity/Obesity.html. http://kim.foresight.gov.uk/Obesity/Obesity.html. Important Clinical Questions.

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Mathematical Modeling of Metabolism and Obesity

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  1. Mathematical Modeling of Metabolism and Obesity Kevin D Hall Laboratory of Biological Modeling NIDDK March 6, 2009

  2. “Systems Modeling” of Obesity http://kim.foresight.gov.uk/Obesity/Obesity.html

  3. http://kim.foresight.gov.uk/Obesity/Obesity.html

  4. Important Clinical Questions • If I adhere to a diet or exercise program, how much weight will I lose? • How much will be Body Fat Loss? • How long will it take? • How can I maintain weight loss over the long-term? • Useful for weight loss goal setting

  5. Food Intake Energy Expenditure Carbohydrate Intake Fat Intake Protein Intake Resting Metabolic Rate Total Energy Expenditure Fuel Selection Carbohydrate Oxidation Fat Oxidation Nitrogen Excretion Glucose Turnover Gluconeogenesis Lipolysis Lipogenesis Protein Turnover Body Weight Lean Mass Fat Mass Body Water Body Composition Metabolic Fluxes Human Metabolism Modeling Physical Activity Mathematical Model of Human Metabolism

  6. DNL GNGp GNGf CI PI FI G F P Fat Ox Carb Ox Prot Ox KD Hall. Am J Physiol 291: E23–E37 (2006).

  7. Model Equations K.D. Hall. Am J Physiol 291: E23–E37 (2006).

  8. CALERIE: LCD group Total Energy Expenditure Resting Metabolic Rate Energy Intake Physical Activity Data from L.K. Heilbronn et al. JAMA 295:1539-48 (2006)

  9. CALERIE: LCD group Fat Mass Change Body Weight Change Data from L.K. Heilbronn et al. JAMA 295:1539-48 (2006)

  10. CALERIE: CR group Total Energy Expenditure Energy Intake Resting Metabolic Rate Physical Activity Data from L.K. Heilbronn et al. JAMA 295:1539-48 (2006)

  11. CALERIE: CR group Fat Mass Change Body Weight Change Data from L.K. Heilbronn et al. JAMA 295:1539-48 (2006)

  12. CALERIE: CR group extrapolation Very Long Time Constant! Fat Mass Change Body Weight Change Data from L.K. Heilbronn et al. JAMA 295:1539-48 (2006)

  13. Weight Maintenance at a New BW • What is the expected change of steady-state body weight for a given dietary intervention?

  14. Weight Maintenance at a New BW • What is the expected change of steady-state body weight for a given dietary intervention? • To maintain a given weight loss, ΔBW, energy intake must equal the new energy expenditure

  15. Weight Maintenance at a New BW • What is the expected change of steady-state body weight for a given dietary intervention? • To maintain a given weight loss, ΔBW, energy intake must equal the new energy expenditure • So, we need to determine how steady-state energy expenditure changes with weight loss

  16. Regression coefficients from RMR data Physical Activity Adaptive Thermogenesis Contributions to Energy Expenditure at Steady State KD Hall and PN Jordan Am. J. Clin. Nutr. 88:1485 (2008)

  17. Fat Fraction of Weight Loss K.D. Hall Br. J. Nutr. 97:1059-63 (2007)

  18. Body Composition Changes R2 = 0.90 KD Hall and PN Jordan Am. J. Clin. Nutr. 88:1485 (2008)

  19. Predicted ΔBW for a Specified Diet Intervention • Combine the nonlinear body composition model with the energy expenditure model: KD Hall and PN Jordan Am. J. Clin. Nutr. 88:1485 (2008)

  20. Body Weight Changes R2 = 0.83 KD Hall and PN Jordan Am. J. Clin. Nutr. 88:1485 (2008)

  21. KD Hall and PN Jordan Am. J. Clin. Nutr. 88:1485 (2008)

  22. Steady-State Weight Loss Variability Initial BW = 82.3 kg Initial BW = 139.5 kg KD Hall and PN Jordan Am. J. Clin. Nutr. 88:1485 (2008)

  23. Summary • Energy expenditure adaptations are required to explain longitudinal weight loss data • Cross-sectional equations are inadequate • Weight loss dynamics have a long time constant (~years) • Higher initial body fat leads to greater steady-state weight loss for the same caloric reduction

  24. Thanks! NIDDK, NIH Peter N Jordan Nick Knuth Carson Chow Pennington Center Eric Ravussin Steve Smith St. Luke’s-Roosevelt Hospital Dympna Gallagher

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