Martin Jansen, Christine Contini, Michael M Hoffmann, Gerhard Puetz
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引用次数: 0
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 (CM) and the dynamics of postprandial lipemia. Blood samples of normolipidemic, hypertriglyceridemic (HTG) 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 modelled 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 modelling 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 HTG 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.
期刊介绍:
The Journal of Lipid Research (JLR) publishes original articles and reviews in the broadly defined area of biological lipids. We encourage the submission of manuscripts relating to lipids, including those addressing problems in biochemistry, molecular biology, structural biology, cell biology, genetics, molecular medicine, clinical medicine and metabolism. Major criteria for acceptance of articles are new insights into mechanisms of lipid function and metabolism and/or genes regulating lipid metabolism along with sound primary experimental data. Interpretation of the data is the authors’ responsibility, and speculation should be labeled as such. Manuscripts that provide new ways of purifying, identifying and quantifying lipids are invited for the Methods section of the Journal. JLR encourages contributions from investigators in all countries, but articles must be submitted in clear and concise English.