Nordenström Jörgen, Thörne Anders, Aberg Wiveca, Carneheim Claes, Olivecrona Thomas
Department of Surgery, Karolinska University Hospital-Solna, Karolinska Institutet, SE-171 76 Stockholm, Sweden.
Metabolism. 2006 Nov;55(11):1443-50. doi: 10.1016/j.metabol.2006.05.004.
In a randomized crossover study, plasma kinetics of 2 different types of fat emulsions were studied in 8 healthy volunteers by using a hypertriglyceridemic clamp technique. The method involves the stabilization of serum triglyceride (TG) concentration during 180 minutes at a predetermined level (4 mmol/L) by adjustment of TG infusion rate by repeated online measurements of serum TG concentration. The fat emulsions under study were a long-chain fatty acid triglyceride (LCT) emulsion (Intralipid 20%, Fresenius Kabi, Sweden) and a structured triglyceride (STG) emulsion (Structolipid 20%, Fresenius Kabi) where medium- and long-chain fatty acids have been interesterified within a TG molecule. The hypertriglyceridemic clamp was found to have acceptable reproducibility when tested in 3 healthy individuals on 2 different occasions, as similar steady-state TG levels were obtained by infusing similar amounts of fat. The average (+/-SEM) TG concentration during the 180-minute clamp was similar for STGs and LCTs (4.0 +/- 0.1 vs 3.9 +/- 0.1 mmol/L; not significant), but the amount of fat that had to be infused was significantly higher during STG than during LCT clamping (0.31 +/- 0.04 vs 0.21 +/- 0.02 g TG per minute; P < .05). Higher serum levels of free fatty acids (1.80 +/- 0.13 vs 0.96 +/- 0.09 mmol/L; P < .05), free glycerol (1.30 +/- 0.07 vs 0.76 +/- 0.08 mmol/L; P < .001), and beta-OH butyrate (1.61 +/- 0.44 vs 1.17 +/- 0.23 mmol/L; not significant) were obtained at the end of the clamp during infusion of STGs compared with LCTs. During infusion of STGs the medium-chain fatty acids octanoic (C:8) and decanoic acid (C:10) constituted approximately half of circulating fatty acids that correspond to the compositional ratio of the emulsion. Plasma lipoprotein lipase (LPL) concentration was higher during STG than during LCT clamping (6.06 +/- 0.62 vs 3.15 +/- 0.40 mU/mL; P < .05), and there was a positive correlation between the mean LPL concentration and the amount of infused TG during the steady-state period (r = 0.58; P < .05). In conclusion, the hypertriglyceridemic clamp method was found to give reproducible results and could be considered for comparison of metabolic clearance properties of different types of fat emulsions. The capacity of healthy subjects to eliminate STGs from blood was greater than for LCTs. An increased LPL activity induced by the higher TG infusion rate may have contributed to the increased metabolic clearance of STGs.
在一项随机交叉研究中，通过使用高甘油三酯钳夹技术，在8名健康志愿者中研究了2种不同类型脂肪乳剂的血浆动力学。该方法包括通过重复在线测量血清甘油三酯浓度来调整甘油三酯输注速率，从而在180分钟内将血清甘油三酯（TG）浓度稳定在预定水平（4 mmol/L）。所研究的脂肪乳剂是长链脂肪酸甘油三酯（LCT）乳剂（英脱利匹特20%，费森尤斯卡比公司，瑞典）和结构化甘油三酯（STG）乳剂（结构脂质20%，费森尤斯卡比公司），其中中链和长链脂肪酸在甘油三酯分子内进行了酯交换。当在3名健康个体的2个不同时间点进行测试时，发现高甘油三酯钳夹具有可接受的重现性，因为通过输注相似量的脂肪可获得相似的稳态TG水平。在180分钟钳夹期间，STG和LCT的平均（±SEM）TG浓度相似（4.0±0.1对3.9±0.1 mmol/L；无显著差异），但在STG钳夹期间必须输注的脂肪量显著高于LCT钳夹期间（每分钟0.31±0.04对0.21±0.02 g TG；P<.05）。与LCT相比，在STG输注钳夹结束时，血清游离脂肪酸（1.80±0.13对0.96±0.09 mmol/L；P<.05）、游离甘油（1.30±0.07对0.76±0.08 mmol/L；P<.001）和β-羟基丁酸（1.61±0.44对1.17±0.23 mmol/L；无显著差异）水平更高。在STG输注期间，中链脂肪酸辛酸（C:8）和癸酸（C:10）约占循环脂肪酸的一半，这与乳剂的组成比例相对应。STG钳夹期间血浆脂蛋白脂肪酶（LPL）浓度高于LCT钳夹期间（6.06±0.62对3.15±0.40 mU/mL；P<.05），并且在稳态期平均LPL浓度与输注的TG量之间存在正相关（r = 0.58；P<.05）。总之，发现高甘油三酯钳夹方法可给出可重现的结果，可用于比较不同类型脂肪乳剂的代谢清除特性。健康受试者从血液中清除STG的能力大于LCT。较高的TG输注速率诱导的LPL活性增加可能有助于STG代谢清除的增加。
