Modeling the postprandial CETP-mediated lipid redistribution between chylomicrons, LDL and HDL.

Abstract

Impaired triglyceride (TG) metabolism is associated with metabolic diseases. Non-steady state dynamics make studying postprandial lipid metabolism challenging. We already introduced a mathematical model to estimate cholesteryl ester transfer protein (CETP)-mediated TG net flux in the fasting state. Here, we expand this model to chylomicrons (CMs) and the dynamics of postprandial lipemia. Blood samples of normolipidemic, hypertriglyceridemic, and hyperchylomicronemic volunteers were drawn at fasting and postprandial state. We separated lipoprotein classes via classical sequential ultracentrifugation. To address CMs, we developed a novel method based on Airfuge® ultracentrifugation. We studied postprandial changes of lipoproteins and their components. CETP-mediated TG redistribution was modeled based on the surface and composition data of respective lipoprotein fractions and validated by corresponding measured values. Our model estimated CETP-mediated TG flux in the fasting and postprandial state with high accuracy. Even in the postprandial condition, TG net flux to LDL/HDL is dominated by VLDL. Separating CM from VLDL and modeling both fractions instead of just using the combined CM + VLDL fraction did only improve the model's accuracy slightly (by less than 7%). The proportion of ApoC3 redistributed from HDL to VLDL in postprandial lipemia is highly correlated with the change of ApoA1 in HDL2b. Our basic model is able to estimate TG redistribution via CETP among lipoproteins in postprandial lipemia of healthy and hypertriglyceridemic subjects. An additional separation of VLDL and CM is not strictly necessary to model postprandial TG flux. Our model makes postprandial lipoprotein metabolism more tangible and may help to study lipoprotein-associated pathologies.