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Investigation of human apoB48 metabolism using a new, integrated non-steady-state model of apoB48 and apoB100 kinetics.
Journal of Internal Medicine ( IF 9.0 ) Pub Date : 2019-03-12 , DOI: 10.1111/joim.12877 E Björnson 1 , C J Packard 2 , M Adiels 1 , L Andersson 1 , N Matikainen 3, 4, 5 , S Söderlund 3, 4 , J Kahri 3, 4 , C Sihlbom 6 , A Thorsell 6 , H Zhou 7 , M-R Taskinen 3, 4 , J Borén 1
Journal of Internal Medicine ( IF 9.0 ) Pub Date : 2019-03-12 , DOI: 10.1111/joim.12877 E Björnson 1 , C J Packard 2 , M Adiels 1 , L Andersson 1 , N Matikainen 3, 4, 5 , S Söderlund 3, 4 , J Kahri 3, 4 , C Sihlbom 6 , A Thorsell 6 , H Zhou 7 , M-R Taskinen 3, 4 , J Borén 1
Affiliation
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BACKGROUND
Triglyceride-rich lipoproteins and their remnants have emerged as major risk factors for cardiovascular disease. New experimental approaches are required that permit simultaneous investigation of the dynamics of chylomicrons (CM) and apoB48 metabolism and of apoB100 in very low-density lipoproteins (VLDL).
METHODS
Mass spectrometric techniques were used to determine the masses and tracer enrichments of apoB48 in the CM, VLDL1 and VLDL2 density intervals. An integrated non-steady-state multicompartmental model was constructed to describe the metabolism of apoB48- and apoB100-containing lipoproteins following a fat-rich meal, as well as during prolonged fasting.
RESULTS
The kinetic model described the metabolism of apoB48 in CM, VLDL1 and VLDL2 . It predicted a low level of basal apoB48 secretion and, during fat absorption, an increment in apoB48 release into not only CM but also directly into VLDL1 and VLDL2 . ApoB48 particles with a long residence time were present in VLDL, and in subjects with high plasma triglycerides, these lipoproteins contributed to apoB48 measured during fasting conditions. Basal apoB48 secretion was about 50 mg day-1 , and the increment during absorption was about 230 mg day-1 . The fractional catabolic rates for apoB48 in VLDL1 and VLDL2 were substantially lower than for apoB48 in CM.
DISCUSSION
This novel non-steady-state model integrates the metabolic properties of both apoB100 and apoB48 and the kinetics of triglyceride. The model is physiologically relevant and provides insight not only into apoB48 release in the basal and postabsorptive states but also into the contribution of the intestine to VLDL pool size and kinetics.
中文翻译：
使用apoB48和apoB100动力学的新的集成非稳态模型研究人apoB48的代谢。
背景技术富含甘油三酸酯的脂蛋白及其残余物已经成为心血管疾病的主要危险因素。需要新的实验方法，以允许同时研究极低密度脂蛋白（VLDL）中乳糜微粒（CM）和apoB48代谢以及apoB100的动力学。方法采用质谱技术确定CM，VLDL1和VLDL2密度区间中apoB48的质量和示踪剂富集。构建了一个集成的非稳态多室模型，以描述富含脂肪的餐后以及长期禁食期间含apoB48和apoB100的脂蛋白的代谢。结果动力学模型描述了载脂蛋白B48在CM，VLDL1和VLDL2中的代谢。它预测了基础apoB48的分泌水平较低，并且在脂肪吸收过程中，apoB48的增加不仅释放到CM中，而且释放到VLDL1和VLDL2中。VLDL中存在具有长停留时间的ApoB48颗粒，在血浆甘油三酸酯含量较高的受试者中，这些脂蛋白对禁食期间测得的apoB48有贡献。基础apoB48分泌约50 mg第1天，吸收期间增加约230 mg day-1。VLDL1和VLDL2中apoB48的分解代谢率明显低于CM中apoB48的分解代谢率。讨论这种新颖的非稳态模型整合了apoB100和apoB48的代谢特性以及甘油三酸酯的动力学。该模型具有生理相关性，不仅提供了对apoB48在基础状态和吸收后状态释放的信息，而且还提供了肠道对VLDL库大小和动力学的贡献的见解。
更新日期：2019-03-13
中文翻译：
使用apoB48和apoB100动力学的新的集成非稳态模型研究人apoB48的代谢。
背景技术富含甘油三酸酯的脂蛋白及其残余物已经成为心血管疾病的主要危险因素。需要新的实验方法，以允许同时研究极低密度脂蛋白（VLDL）中乳糜微粒（CM）和apoB48代谢以及apoB100的动力学。方法采用质谱技术确定CM，VLDL1和VLDL2密度区间中apoB48的质量和示踪剂富集。构建了一个集成的非稳态多室模型，以描述富含脂肪的餐后以及长期禁食期间含apoB48和apoB100的脂蛋白的代谢。结果动力学模型描述了载脂蛋白B48在CM，VLDL1和VLDL2中的代谢。它预测了基础apoB48的分泌水平较低，并且在脂肪吸收过程中，apoB48的增加不仅释放到CM中，而且释放到VLDL1和VLDL2中。VLDL中存在具有长停留时间的ApoB48颗粒，在血浆甘油三酸酯含量较高的受试者中，这些脂蛋白对禁食期间测得的apoB48有贡献。基础apoB48分泌约50 mg第1天，吸收期间增加约230 mg day-1。VLDL1和VLDL2中apoB48的分解代谢率明显低于CM中apoB48的分解代谢率。讨论这种新颖的非稳态模型整合了apoB100和apoB48的代谢特性以及甘油三酸酯的动力学。该模型具有生理相关性，不仅提供了对apoB48在基础状态和吸收后状态释放的信息，而且还提供了肠道对VLDL库大小和动力学的贡献的见解。
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