Inhibitors of hepatic microsomal triacylglycerol hydrolase decrease very low density lipoprotein secretion
Inhibitors of hepatic microsomal triacylglycerol hydrolase decrease very low density lipoprotein secretion
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DOI：
10.1096/fj.02-0728fje
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发表时间：
2003-07-01
期刊：
影响因子：
4.8
通讯作者：
Lehner, R
中科院分区：
文献类型：
--
作者：
Gilham, D;Ho, S;Lehner, R
循环中富含三酰甘油（TG）的极低密度脂蛋白（VLDL）和载脂蛋白B-100（apo B-100）水平升高是冠状动脉疾病的独立危险因素。三酰甘油水解酶催化细胞质TG储存的动员。为了检验这一假设，即酶发挥了作用，在提供核心脂质的装配极低密度脂蛋白，我们抑制了脂肪酶的活性在原代大鼠肝细胞和分析脂质和载脂蛋白B的合成和分泌。脂解的抑制导致TG分泌的急剧减少。此外，胆固醇酯和磷脂酰胆碱的分泌显著减少。分泌的载脂蛋白的分析表明，apoB-100的分泌是更敏感的脂肪酶抑制比apoB-48分泌，可能是因为apoB-48的能力，分泌作为一个相对脂质贫乏的颗粒。结果与用三酰甘油水解酶cDNA转染的肝癌细胞中观察到的apoB-100优先脂化的结果一致。总之，我们的研究结果提供的证据表明，抑制细胞内TG水解显着降低载脂蛋白B-100的分泌，并建议，三酰甘油水解酶可能是一个合适的药理学目标，努力降低血脂水平。
The presence of elevated circulating triacylglycerol (TG)-rich very low density lipoprotein (VLDL) and apolipoprotein B-100 (apoB-100) levels represents an independent risk factor for coronary artery disease. Triacylglycerol hydrolase catalyzes the mobilization of cytoplasmic TG stores. To test the hypothesis that the enzyme plays a role in the provision of core lipids for the assembly of VLDL, we inhibited the lipase activity in primary rat hepatocytes and analyzed lipid and apoB synthesis and secretion. Inhibition of lipolysis resulted in a dramatic decrease in secretion of TGs. In addition, secretion of cholesteryl ester and phosphatidylcholine was substantially decreased. Analysis of secreted apolipoproteins indicated that apoB-100 secretion was much more sensitive to lipase inhibition than was apoB-48 secretion, perhaps because of the ability of apoB-48 to be secreted as a relatively lipid-poor particle. The results agreed with those obtained with hepatoma cells transfected with triacylglycerol hydrolase cDNA, in which preferential lipidation of apoB-100 was observed. Together, our findings provide evidence that inhibition of intracellular TG hydrolysis significantly decreases apoB-100 secretion and suggest that triacylglycerol hydrolase may be a suitable pharmacological target in efforts to lower plasma lipid levels.