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苯巴比妥和肝素对脂蛋白脂肪酶调节的生物学意义。

The biological significance of lipoprotein lipase modulation by phenobarbital and heparin.

作者信息

Goldberg D M, Parkes J G, Chajek-Shaul T, Bglibter N

机构信息

Department of Clinical Biochemistry, University of Toronto, Canada.

出版信息

Adv Enzyme Regul. 1991;31:195-221. doi: 10.1016/0065-2571(91)90014-d.

DOI:10.1016/0065-2571(91)90014-d
PMID:1877388
Abstract

When confluent cultures of 3T3 F442A cells were treated with insulin, differentiation occurred within 6 days as indicated by LPL secretion followed by increased intracellular levels of protein and triacylglycerol. PB increased LPL secretion 2- to 3-fold and intracellular LPL 3- to 10-fold in a time-dependent manner; these increments were less in proportion to the length of the time interval between confluence and initiation of PB treatment. These results are consistent with the notion that PB promotes conversion of adipocyte precursors to mature adipocytes by increasing the proportion of the former that become susceptible to the differentiating stimulus. Human subjects treated with heparin by continuous i.v. infusion over 4 days showed an initial decrease in serum triacylglycerol concentration in response to the initial bolus injection, accompanied by sharp increases in circulating LPL and HTGL, but the triacylglycerol concentration returned to normal within 24 hr. Rats infused with heparin by means of peritoneal implantation of osmotic minipumps demonstrated dose-dependent increases in circulating LPL, accompanied by reduction in heart muscle LPL but inconsistent changes in other tissues examined. Heparin had no effect on the clearance of circulating LPL but did reduce the total body pool of endothelial-bound enzyme. No changes in fasting triacylglycerol and free glycerol were observed, but exogenous VLDL were cleared at a faster rate in heparinized animals. Since the latter also manifested a decrease in de novo fatty acid synthesis, it seems that the heparinized rat is able to maintain circulating levels of triacylglycerol by efficient re-esterification of preformed fatty acids despite the enhanced lipolysis consequent upon higher plasma LPL activity.

摘要

当用胰岛素处理3T3 F442A细胞的汇合培养物时,6天内发生分化,这表现为脂蛋白脂肪酶(LPL)分泌增加,随后细胞内蛋白质和三酰甘油水平升高。苯巴比妥(PB)以时间依赖性方式使LPL分泌增加2至3倍,细胞内LPL增加3至10倍;这些增加与汇合和开始PB处理之间的时间间隔长度的比例较小。这些结果与以下观点一致,即PB通过增加易受分化刺激的脂肪细胞前体的比例来促进其向成熟脂肪细胞的转化。通过连续静脉输注肝素4天治疗的人类受试者,在初始推注注射后血清三酰甘油浓度最初降低,同时循环LPL和肝甘油三酯脂肪酶(HTGL)急剧增加,但三酰甘油浓度在24小时内恢复正常。通过渗透性微型泵腹膜植入给予肝素的大鼠表现出循环LPL的剂量依赖性增加,同时心肌LPL减少,但在所检查的其他组织中变化不一致。肝素对循环LPL的清除没有影响,但确实减少了内皮结合酶的全身储备。未观察到空腹三酰甘油和游离甘油的变化,但在肝素化动物中外源性极低密度脂蛋白(VLDL)的清除速度更快。由于后者还表现出从头脂肪酸合成减少,似乎肝素化大鼠能够通过有效重新酯化预先形成的脂肪酸来维持三酰甘油的循环水平,尽管由于较高的血浆LPL活性导致脂解增强。

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