Prediction of murine liver kinetics from plasma lipoprotein distributions

The role of liver in lipid metabolism has been studied extensively. However, due to the complexity of in vivo liver measurements, many experimental efforts have focused on studying liver responses by measuring plasma lipoprotein distributions. The characteristics of these distributions co‐determine several metabolic disease risks and depend on production, clearance and remodeling of lipoproteins, all regulated by the liver. A challenge remains to determine the kinetics and distribution of fluxes in the complex network of metabolic pathways in the liver that give rise to these distributions. Here, we report on a computational approach to obtain this information. A computational multi‐compartment model was constructed including reactions representing lipogenesis, cholesterol synthesis, fatty acid handling and lipoprotein metabolism in liver and lipoprotein remodeling in plasma. We consider a high‐resolution grid of different lipoprotein classes, from which lipoprotein distributions are calculated. Novel in this approach is the inclusion of lipoprotein kinetics, yielding additional information to constrain internal liver predictions and vice versa. In future, the model will be used to study the dynamic interactive behavior of plasma lipoprotein metabolism and metabolic pathways in murine liver for different physiological conditions. Funded by the Netherlands Consortium for Systems Biology.