Jansen Martin, Contini Christine, Hoffmann Michael M, Puetz Gerhard
Institute of Clinical Chemistry and Laboratory Medicine, Medical Centre-University of Freiburg, Freiburg im Breisgau, Germany; Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany.
Institute of Clinical Chemistry and Laboratory Medicine, Medical Centre-University of Freiburg, Freiburg im Breisgau, Germany; Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany.
J Lipid Res. 2025 Jul;66(7):100847. doi: 10.1016/j.jlr.2025.100847. Epub 2025 Jun 23.
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.
甘油三酯（TG）代谢受损与代谢性疾病相关。非稳态动力学使得研究餐后脂质代谢具有挑战性。我们已经引入了一个数学模型来估计空腹状态下胆固醇酯转移蛋白（CETP）介导的TG净通量。在此，我们将该模型扩展至乳糜微粒（CM）以及餐后血脂异常的动力学。在空腹和餐后状态下采集了血脂正常、高甘油三酯血症和高乳糜微粒血症志愿者的血样。我们通过经典的连续超速离心法分离脂蛋白类别。为了研究CM，我们基于空气离心机®超速离心法开发了一种新方法。我们研究了脂蛋白及其成分的餐后变化。基于各脂蛋白组分的表面和组成数据对CETP介导的TG重新分布进行建模，并通过相应的测量值进行验证。我们的模型能够高精度地估计空腹和餐后状态下CETP介导的TG通量。即使在餐后状态下，向低密度脂蛋白/高密度脂蛋白的TG净通量仍以极低密度脂蛋白为主。将CM与极低密度脂蛋白分离并对两个组分进行建模，而不是仅使用CM + 极低密度脂蛋白的合并组分，仅略微提高了模型的准确性（提高不到7%）。餐后血脂异常时从高密度脂蛋白重新分布至极低密度脂蛋白的载脂蛋白C3比例与高密度脂蛋白2b中载脂蛋白A1的变化高度相关。我们的基础模型能够估计健康和高甘油三酯血症受试者餐后血脂异常中通过CETP在脂蛋白之间进行的TG重新分布。对餐后TG通量进行建模时，并非严格需要额外分离极低密度脂蛋白和CM。我们的模型使餐后脂蛋白代谢更易于理解，可能有助于研究与脂蛋白相关的病理学。
