Green M H, Faulkner P L, Green J B
Nutrition Department, Pennsylvania State University, University Park, 16802.
Prog Food Nutr Sci. 1988;12(3):255-78.
Model-based compartmental analysis was used to interpret data on temporal changes in plasma triglyceride (TG) response to a chronic infusion of chylomicrons (CM) in the rat. Male rats were fed purified diets which varied in fat load [L = 10% (w/w), H = 30%] and P/S ratio (P = 4.6, S = 0.2). Lymph CM isolated from donor rats which were absorbing the P or S fat were infused into recipients for 8 h on 3 consecutive days: on d 1 and 3, CM infusion rate reflected the fat content of the previous diet and on d 2, the other load; the infusion replaced dietary fat. Serial plasma samples from each period were analyzed for TG concentration; TG distribution in plasma lipoproteins and liver lipids was measured after d 3. To describe observed group average data, a compartmental model was developed using the Simulation, Analysis and Modeling computer program. Two compartments were needed in plasma (CM vs nonCM TG); each had 2 outputs: removal of TG-fatty acids by lipoprotein lipase (LPL) and uptake of remnant lipoproteins by the liver. After a delay in the liver, there were 3 fates for TG-derived fatty acids: oxidation, retention, or secretion in very low density lipoproteins. Simulation of changes in the rate constant for total CM TG turnover indicated that the basal level of LPL rose rapidly and dramatically in response to TG infusion; the rise was higher for H vs L. After 3-5 h, apparent LPL activity decreased. Simulation of the rate of CM TG turnover indicated that the turnover rate rose immediately after infusion began to levels higher than the infusion rate, and then came into a slight negative balance. Although the observed data could be qualitatively described based on current understanding of TG metabolism, application of model-based compartmental analysis generated testable hypotheses about quantitative aspects of the system dynamics.
基于模型的房室分析被用于解释大鼠慢性输注乳糜微粒（CM）后血浆甘油三酯（TG）反应的时间变化数据。雄性大鼠喂食脂肪含量[L = 10%（w/w），H = 30%]和P/S比（P = 4.6，S = 0.2）不同的纯化饮食。从吸收P或S脂肪的供体大鼠分离的淋巴CM连续3天输注到受体大鼠体内8小时：在第1天和第3天，CM输注速率反映前一天饮食的脂肪含量，在第2天，反映另一种脂肪含量；输注替代了饮食脂肪。分析每个时间段的系列血浆样本的TG浓度；在第3天后测量血浆脂蛋白和肝脏脂质中的TG分布。为了描述观察到的组平均数据，使用模拟、分析和建模计算机程序开发了一个房室模型。血浆中需要两个房室（CM与非CM TG）；每个房室有2个输出：脂蛋白脂肪酶（LPL）去除TG-脂肪酸和肝脏摄取残余脂蛋白。在肝脏有一个延迟后，TG衍生脂肪酸有3种去向：氧化、保留或分泌到极低密度脂蛋白中。总CM TG周转速率常数变化的模拟表明，LPL的基础水平在TG输注后迅速显著上升；H组比L组上升更高。3 - 5小时后，表观LPL活性下降。CM TG周转速率的模拟表明，输注开始后周转速率立即上升到高于输注速率的水平，然后进入轻微的负平衡。尽管基于目前对TG代谢的理解可以定性描述观察到的数据，但基于模型的房室分析的应用产生了关于系统动力学定量方面的可检验假设。
