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Centre for Medical Systems Biology

Centre for Medical Systems Biology. Jan Bert van Klinken, LUMC. Introduction. Aim Development of a mathematical model of whole-body metabolism, in relation to metabolic syndrome (obesity, dyslipidemia, high blood pressure, insulin resistance,...) At LUMC focus on whole-body level.

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Centre for Medical Systems Biology

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  1. Centre for Medical Systems Biology Jan Bert van Klinken, LUMC

  2. Introduction Aim Development of a mathematical model of whole-body metabolism, in relation to metabolic syndrome(obesity, dyslipidemia, high blood pressure, insulin resistance,...) At LUMC focus on whole-body level. At TU/e focus on cellular level. ? Modelling Whole Body Metabolism

  3. The hyperinsulinemic-euglycemic clamp Insulin resistance: a condition in which normal amounts of insulin are inadequate to produce a normal insulin response in muscle, liver and fat cells GLUCOSE INFUSION Plasma glucose PERIPHERAL TISSUES - LIVER + INSULIN INFUSION Modelling Whole Body Metabolism

  4. Indirect Calorimetry Metabolic flexibility: the ability to adapt fuel selection to fuel availability glucose C6H12O6 + 6O2 6CO2 + 6H2O RER = 1.0 tripalmitin 2 C51H98O6 + 145O2 102CO2 + 98H2O RER = 0.7 1 Fat Carb 0.7 Modelling Whole Body Metabolism

  5. Modelling Approach Mathematical model will be based on that of Hall, which explains at a macrolevel how changes in body weight and composition result from changes in food intake. Existing model will be extended with more detailed regulation mechanisms for glucose and fat homeostasis and organ specificity. Hall (2006) Am J Physiol Endocrinol Metab Modelling Whole Body Metabolism

  6. Modelling Approach In order to be better able to validate the mathematical model, existing experimental techniques and methods for data analysis are being optimised. - relate time patterns in variables measured by metabolic cage (food intake, physical activity, O2 and CO2 exchange) by means of digital signal processing techniques. - refine calculations of macronutrient oxidation rates (from O2 and CO2 exchange) for specific diet compositions, such that whole-body energy balance can be deduced. - perform clamp and other tracer experiments with stable isotopes in order to get a more comprehensive picture of macronutrient flows and their regulation. Modelling Whole Body Metabolism

  7. Summary * Main focus in our Systems Biology approach lies on quantitative understanding * Dynamic mathematical models simple (typically few dynamic variables) * Heterogeneous experimental data: metabolic cage, dexa scan, clamp, tracer experiments, Western blot * Broad range of analysis techniques: digital signal processing, statistics, stoichiometric analysis (simulation, control analysis) Modelling Whole Body Metabolism

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