Preiss-Landl Karina, Zimmermann Robert, Hämmerle Günter, Zechner Rudolf
Institute of Molecular Bioloogy, Biochemistry and Microbiology, Karl-Frasnzens-University, Graz, Heinrichstrasse 31a, A-8010 Graz, Austria.
Curr Opin Lipidol. 2002 Oct;13(5):471-81. doi: 10.1097/00041433-200210000-00002.
The aim of this review is to summarize and discuss recent advances in the understanding of the physiological role of lipoprotein lipase in lipid and energy metabolism.
Studies on the transcriptional and the posttranscriptional level of lipoprotein lipase expression have provided new insights into the complex mechanisms that are involved in the regulation of the enzyme. Additionally a large body of evidence from both human studies and animal models suggests that the level of lipoprotein lipase expression in a given tissue is the rate limiting process for the uptake of triglyceride derived fatty acids. Imbalances in the partitioning of fatty acids among peripheral tissues have major metabolic consequences. For example, in mice both decreased lipoprotein lipase activities in adipose tissue and increased activity in muscle are associated with resistance to obesity; lack of lipoprotein lipase activity in macrophages is correlated with a decreased susceptibility to develop atherosclerotic lesions and overexpression of the enzyme in muscle is associated with increased blood glucose levels and insulin resistance.
Considering the central role of lipoprotein lipase in energy metabolism it is a reasonable goal to discover and develop new drugs that affect the tissue specific expression pattern of the enzyme.
本综述旨在总结和讨论脂蛋白脂肪酶在脂质和能量代谢中的生理作用的最新研究进展。
关于脂蛋白脂肪酶表达的转录和转录后水平的研究为参与该酶调控的复杂机制提供了新见解。此外，来自人体研究和动物模型的大量证据表明，特定组织中脂蛋白脂肪酶的表达水平是甘油三酯衍生脂肪酸摄取的限速过程。外周组织间脂肪酸分配失衡会产生重大代谢后果。例如，在小鼠中，脂肪组织中脂蛋白脂肪酶活性降低和肌肉中活性增加均与肥胖抵抗相关；巨噬细胞中缺乏脂蛋白脂肪酶活性与动脉粥样硬化病变易感性降低相关，而该酶在肌肉中过表达与血糖水平升高和胰岛素抵抗相关。
鉴于脂蛋白脂肪酶在能量代谢中的核心作用，发现和开发影响该酶组织特异性表达模式的新药是一个合理目标。
