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Overall aim: Development of mathematical models describing lipid and carbohydrate metabolism at whole body and organ specific level in mice Leiden University.

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Presentation on theme: "Overall aim: Development of mathematical models describing lipid and carbohydrate metabolism at whole body and organ specific level in mice Leiden University."— Presentation transcript:

0 Computational Modeling of Hepatic Lipid and Lipoprotein Metabolism
NCSB / NBIC Modelers-Bioinformatics Meeting

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2 Overall aim: Development of mathematical models describing lipid and carbohydrate metabolism at whole body and organ specific level in mice Leiden University Medical Center BioModeling & bioInformatics Biomedical NMR

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4

5 FFA triglyceride cholesterol ester HDL LDL IDL VLDL chylomicron
remnants LDL IDL VLDL triglyceride cholesterol ester

6 Véniant et al.

7 Liang et al. Zhang et al. Boogaerts et al. Grefhorst et al.
TG TG Grefhorst et al. Davis et al. Dixon et al. TG TG TG Millar et al. Wong et al. Horton et al.

8 Part I Part II FA metabolism Lipogenesis Lipolysis Ketogenesis
apoB metabolism Remnant catabolism NEFA

9 Liver Peripheral G3P Glycerol FA FA LPA FA PA MG FA DAG C FA FA FA FA
GK G3P Glycerol Liver FA G3P GPAT / AGPAT FA LPA MGL FA MGK GPAT / AGPAT PA MG PPAP2 MGAT HSL:FABP4 DGK FA DAG C FAS FA FA FA FA FA DGAT1 TGH HSL:FABP4 ACAT HSL:FABP4 TG / CE / Glycerol TG CE FA FA Apo B DGAT2 MTP TG CE Apo B Lipoprotein Type Matrix FFA Peripheral

10 Liver Peripheral G3P Glycerol FA FA LPA FA PA MG FA DAG C FA FA FA FA
GK G3P Glycerol Liver FA G3P GPAT / AGPAT FA LPA MGL FA MGK GPAT / AGPAT PA MG PPAP2 MGAT HSL:FABP4 DGK FA DAG C FAS FA FA FA FA FA DGAT1 TGH HSL:FABP4 ACAT HSL:FABP4 TG / CE / Glycerol TG CE FA FA Apo B DGAT2 MTP TG CE Apo B Lipoprotein Type Matrix FFA Peripheral

11 Liver Peripheral G3P Glycerol FA FA LPA FA PA MG FA DAG C FA FA FA FA
GK G3P Glycerol Liver FA G3P GPAT / AGPAT FA LPA MGL FA MGK GPAT / AGPAT PA MG PPAP2 MGAT HSL:FABP4 DGK FA DAG C FAS FA FA FA FA FA DGAT1 TGH HSL:FABP4 ACAT HSL:FABP4 TG / CE / Glycerol TG CE FA FA Apo B DGAT2 MTP TG CE Apo B Lipoprotein Type Matrix FFA Peripheral

12 Quantitative data generation
Literature Exhaustingly searching for kinetic parameters and specie concentrations Text mining techniques to infer quantitative information (PHASAR / BioMeta) Inferring pathway topologies in a more structured way Bijland et al. parameter estimation

13 Liver Peripheral G3P Glycerol FA FA LPA FA PA MG FA DAG C FA FA FA FA
GK G3P Glycerol Liver FA G3P GPAT / AGPAT FA LPA MGL FA MGK GPAT / AGPAT PA MG PPAP2 MGAT HSL:FABP4 DGK FA DAG C FAS FA FA FA FA FA DGAT1 TGH HSL:FABP4 ACAT HSL:FABP4 TG / CE / Glycerol TG CE FA FA Apo B DGAT2 MTP TG CE Apo B Lipoprotein Type Matrix FFA Peripheral

14 Different lipoprotein types
Based on triglyceride and cholesterol content Color represents concentration of lipoprotein type Cholesterol: 1000 Triglyceride: 5000 triglyceride  VLDL production particle uptake content transfer hydrolysis cholesterol 

15 VLDL production Particle uptake Hydrolysis CETP triglyceride 
Apo B TG CE VLDL production Particle uptake Hydrolysis CETP 10 9 triglyceride  cholesterol 

16 VLDL production Particle uptake Hydrolysis CETP triglyceride 
9 10 triglyceride  cholesterol 

17 VLDL production Particle uptake Hydrolysis CETP triglyceride 
9 10 triglyceride  1 cholesterol 

18 VLDL production Particle uptake Hydrolysis CETP triglyceride 
1 9 10 9 10 triglyceride  1 cholesterol 

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20 Acknowledgements Peter Hilbers Natal van Riel Jeroen Jeneson
Joep Vanlier Joep Schmitz Çeylan Cölmekçi Ko Willems van Dijk Jan Bert van Klinken Sjoerd van den Berg Silvia Bijland


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