Dietary saturated triacylglycerols suppress hepatic low density lipoprotein receptor activity in the hamster.

Dietary saturated triacylglycerols suppress hepatic low density lipoprotein receptor activity in the hamster.
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DOI:
10.1073/pnas.82.13.4526
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发表时间:
1985-07
影响因子:
11.1
通讯作者:
D. Spady;J. Dietschy
D. Spady;J. Dietschy
中科院分区:
综合性期刊1区
文献类型:
--
作者:
D. Spady;J. Dietschy

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肝脏在调节低密度脂蛋白(LDL)的循环水平中起着关键作用,因为它既是这类脂蛋白的生产场所,也是降解这类脂蛋白的主要器官。在这项研究中,饲养多不饱和或饱和三酰甘油受体依赖性和受体非依赖性的肝脏LDL摄取的影响进行了测量,在仓鼠体内。在对照动物中,受体依赖性LDL转运表现出85 mg/dl(血浆LDL-胆固醇浓度)的表观Km值,并达到131微克LDL-胆固醇/小时/克的最大转运速度,而受体非依赖性摄取增加作为血浆LDL水平的线性函数。因此,在正常血浆LDL-胆固醇浓度下,LDL的肝脏清除率分别等于120和9微升/小时/克受体依赖性和受体非依赖性机制。随着血浆LDL-胆固醇的增加,受体依赖性(而非受体非依赖性)组分下降。当胆固醇(0.12%)单独或与多不饱和三酰甘油组合喂养30天时,受体依赖性清除率降低至36-42微升/小时/克,而胆固醇加饱和三酰甘油的喂养基本上消除了受体依赖性LDL摄取(5微升/小时/克)。当比较适当的动力学曲线,这些研究结果表明,受体介导的低密度脂蛋白转运抑制约等于30%的胆固醇单独喂养,这是不受多不饱和甘油三酯的饮食。与此相反,受体依赖性摄取抑制约等于90%的饱和甘油三酯的摄入量。与多不饱和三酰甘油相比,饱和脂质的摄入还与血浆LDL-胆固醇浓度显著升高和肝脏中胆固醇酯水平降低相关。
The liver plays a key role in the regulation of circulating levels of low density lipoproteins (LDL) because it is both the site for the production of and the major organ for the degradation of this class of lipoproteins. In this study, the effects of feeding polyunsaturated or saturated triacylglycerols on receptor-dependent and receptor-independent hepatic LDL uptake were measured in vivo in the hamster. In control animals, receptor-dependent LDL transport manifested an apparent Km value of 85 mg/dl (plasma LDL-cholesterol concentration) and reached a maximum transport velocity of 131 micrograms of LDL-cholesterol/hr per g, whereas receptor-independent uptake increased as a linear function of plasma LDL levels. Thus, at normal plasma LDL-cholesterol concentrations, the hepatic clearance rate of LDL equaled 120 and 9 microliter/hr per g by receptor-dependent and receptor-independent mechanisms, respectively. As the plasma LDL-cholesterol was increased, the receptor-dependent (but not the receptor-independent) component declined. When cholesterol (0.12%) alone or in combination with polyunsaturated triacylglycerols was fed for 30 days, receptor-dependent clearance was reduced to 36-42 microliter/hr per g, whereas feeding of cholesterol plus saturated triacylglycerols essentially abolished receptor-dependent LDL uptake (5 microliter/hr per g). When compared to the appropriate kinetic curves, these findings indicated that receptor-mediated LDL transport was suppressed approximately equal to 30% by cholesterol feeding alone and this was unaffected by the addition of polyunsaturated triacylglycerols to the diet. In contrast, receptor-dependent uptake was suppressed approximately equal to 90% by the intake of saturated triacylglycerols. As compared to polyunsaturated triacylglycerols, the intake of saturated lipids was also associated with significantly higher plasma LDL-cholesterol concentrations and lower levels of cholesteryl esters in the liver.