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Computational Modeling of Hepatic Lipid and Lipoprotein Metabolism NCSB / NBIC Modelers-Bioinformatics Meeting 26-02-2010.

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Presentation on theme: "Computational Modeling of Hepatic Lipid and Lipoprotein Metabolism NCSB / NBIC Modelers-Bioinformatics Meeting 26-02-2010."— Presentation transcript:

1 Computational Modeling of Hepatic Lipid and Lipoprotein Metabolism NCSB / NBIC Modelers-Bioinformatics Meeting 26-02-2010

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3 Overall aim: Development of mathematical models describing lipid and carbohydrate metabolism at whole body and organ specific level in mice Leiden University Medical CenterBioModeling & bioInformaticsBiomedical NMR

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6 triglyceride cholesterol ester VLDL IDL LDL FFA HDL chylomicron remnants

7 Véniant et al.

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

9 FA metabolism Lipogenesis Lipolysis Ketogenesis apoB metabolism Remnant catabolism NEFA Part IPart II

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

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

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

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

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

15 cholesterol  triglyceride  0 1000 2000 0 5000 10000 Cholesterol: 1000 Triglyceride: 5000 particle uptake hydrolysis Different lipoprotein types −Based on triglyceride and cholesterol content −Color represents concentration of lipoprotein type content transfer VLDL production

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

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

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

19 cholesterol  triglyceride  10 1 99 1 VLDL production Particle uptake Hydrolysis CETP

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21 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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