模拟餐后CETP介导的乳糜微粒、LDL和HDL之间的脂质再分布。

IF 5 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Martin Jansen, Christine Contini, Michael M Hoffmann, Gerhard Puetz
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引用次数: 0

摘要

甘油三酯代谢受损与代谢性疾病有关。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。在这里,我们将这个模型扩展到乳糜微粒(CM)和餐后血脂的动力学。正常血脂、高甘油三酯血症(HTG)和高乳糜血症志愿者分别在空腹和餐后状态抽取血样。我们通过经典的顺序超离心分离脂蛋白类。为了解决CMs问题,我们开发了一种基于Airfuge®超离心的新方法。我们研究了餐后脂蛋白及其组分的变化。cetp介导的TG重分布基于各自脂蛋白组分的表面和组成数据进行建模,并通过相应的测量值进行验证。我们的模型在空腹和餐后状态下以高精度估计cetp介导的TG通量。即使在餐后状态下,TG对LDL/HDL的净通量也由VLDL主导。将CM从VLDL中分离出来并对这两个部分进行建模,而不是仅仅使用CM+VLDL的组合部分,只略微提高了模型的准确性(不到7%)。餐后脂血症中ApoA1在HDL2b中的变化与apo3从HDL到VLDL再分布的比例高度相关。我们的基本模型能够通过CETP在健康和HTG受试者餐后血脂中的脂蛋白中估计TG的再分布。VLDL和CM的额外分离对于模拟餐后TG通量并不是严格必要的。我们的模型使餐后脂蛋白代谢更加有形,并可能有助于研究脂蛋白相关病理。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Modelling the post prandial CETP mediated lipid-redistribution between chylomicrons, LDL and HDL.

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.

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来源期刊
Journal of Lipid Research
Journal of Lipid Research 生物-生化与分子生物学
CiteScore
11.10
自引率
4.60%
发文量
146
审稿时长
41 days
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.
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