KINETIC STUDIES OF PLASMA FREE FATTY ACID AND TRIGLYCERIDE METABOLISM IN MAN

KINETIC STUDIES OF PLASMA FREE FATTY ACID AND TRIGLYCERIDE METABOLISM IN MAN
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DOI:
10.1172/jci106122
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发表时间:
1969-01-01
影响因子:
15.9
通讯作者:
STEINBERG, D
STEINBERG, D
中科院分区:
医学1区
文献类型:
--
作者:
EATON, RP;BERMAN, M;STEINBERG, D

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在7例脂代谢正常、1例完全性脂肪代谢障碍和1例家族性高脂血症(V型)患者中研究了游离脂肪酸(FFA)和甘油三酯脂肪酸(TGFA)的血浆转运。研究进行后,静脉注射放射性FFA,脂蛋白先前在体外标记的甘油三酯moiety,或both.Computer技术被用来评估一系列的多房室模型,并提出了一个通用模型,产生最佳拟合FFA和TGFA的实验数据。结果表明,在正常受试者中,多达20-30%的FFA离开血浆室被转运到交换的血管外池,并迅速重新进入血浆池作为FFA。正常人FFA从血浆到组织的不可逆输送速率平均为358 μEq/min。脂肪代谢障碍患者,尽管实际上没有脂肪组织(尸检证实),血浆FFA浓度和总FFA运输,均超过正常的两倍。在4名正常对照中,总TGFA转运范围为25至81 μEq/min。在V型糖尿病患者中,TGFA周转的速率常数非常小,以至于无法根据现有数据对总转运进行定量; TGFA的半衰期超过500分钟。在两名正常受试者中注射了用三油酸甘油酯-14 C体外标记的自体脂蛋白并同时给予油酸-3H,结果表明,体外标记样品中TGFA消失的时间过程与注射FFA合成的生理标记脂蛋白TGFA几乎完全一致(如通过使用相同的多房室模型和相同的速率常数同时拟合两组数据所证明的)。注射体外标记TGFA的血浆后,血浆FFA组分中出现显著的放射性。据估计,在以这种方式研究的两个正常受试者中,多达50%的总TGFA转运经历了快速且相当直接的转化为FFA。动力学数据表明,TGFA转化为FFA之前没有任何广泛的稀释,例如与组织甘油三酯储存完全混合。图片
Plasma transport of free fatty acids (FFA) and triglyceride fatty acids (TGFA) was studied in seven subjects with normal lipid metabolism, one case of total lipodystrophy, and one case of familial hyperlipemia (Type V). Studies were carried out after intravenous injection of radioactive FFA, of lipoproteins previously labeled in vitro in the triglyceride moiety, or both.Computer techniques were used to evaluate a series of multicompartmental models, and a general model is proposed that yields optimum fitting of experimental data for both FFA and TGFA. The results show that as much as 20-30% of FFA leaving the plasma compartment in normal subjects is transported to an exchanging extravascular pool and quickly reenters the plasma pool as FFA. The rate of irreversible delivery of FFA from plasma to tissues averaged 358 μEq/min in normals. The lipodystrophy patient, despite the virtual absence of adipose tissue (confirmed at autopsy), had a plasma FFA concentration and a total FFA transport, both more than twice normal. Total TGFA transport ranged from 25 to 81 μEq/min in four normal controls. The rate constant for TGFA turnover in the patient with Type V hyperlipemia was so small that total transport could not be quantified from the data available; the TGFA half-life was over 500 min.In two normal subjects given injections of autologous lipoproteins labeled in vitro with triolein-14C and simultaneously given oleic acid-3H, it was shown that the time course for the disappearance of the TGFA in the in vitro labeled samples conformed almost exactly to that of the physiologically labeled lipoprotein TGFA synthesized from injected FFA (as evidenced by the simultaneous fitting of both sets of data using the same multicompartmental model and the same rate constants). Radioactivity appeared in the plasma FFA fraction at a significant rate after injection of plasma labeled in vitro with TGFA. It was estimated that as much as 50% of the total TGFA transported underwent rapid and rather direct conversion to FFA in the two normal subjects studied this way. The kinetic data suggest that such conversion of TGFA to FFA was not preceded by any extensive dilution, such as would result from complete mixing with tissue triglyceride stores.Images