Hussain M Mahmood, Nijstad Niels, Franceschini Lisa
Departments of Cell Biology and Pediatrics, The State University of New York, Downstate Medical Center, 450 Clarkson Ave, Brooklyn, NY 11203, USA.
Clin Lipidol. 2011 Jun;6(3):293-303. doi: 10.2217/clp.11.21.
Microsomal triglyceride transfer protein (MTP) facilitates the transport of dietary and endogenous fat by the intestine and liver by assisting in the assembly and secretion of triglyceride-rich apolipoprotein B-containing lipoproteins. Higher concentrations of apolipoprotein B lipoproteins predispose individuals to various cardiovascular and metabolic diseases such as atherosclerosis, diabetes, obesity and the metabolic syndrome. These can potentially be avoided by reducing MTP activity. In this article, we discuss regulation of MTP during development, cellular differentiation and diurnal variation. Furthermore, we focus on the regulation of MTP that occurs at transcriptional, post-transcriptional and post-translational levels. Transcriptional regulation of MTP depends on a few highly conserved cis-elements in the promoter. Several transcription factors that bind to these elements and either increase or decrease MTP expression have been identified. Additionally, MTP is regulated by macronutrients, hormones and other factors. This article will address the many ways in which MTP is regulated and advance the idea that reducing MTP levels, rather than its inhibition, might be an option to lower plasma lipids.
微粒体甘油三酯转运蛋白(MTP)通过协助富含甘油三酯的载脂蛋白B脂蛋白的组装和分泌,促进肠道和肝脏对膳食脂肪和内源性脂肪的转运。较高浓度的载脂蛋白B脂蛋白使个体易患各种心血管和代谢疾病,如动脉粥样硬化、糖尿病、肥胖症和代谢综合征。通过降低MTP活性,这些疾病有可能被避免。在本文中,我们讨论了MTP在发育、细胞分化和昼夜变化过程中的调节。此外,我们重点关注MTP在转录、转录后和翻译后水平上的调节。MTP的转录调节取决于启动子中一些高度保守的顺式元件。已经鉴定出几种与这些元件结合并增加或降低MTP表达的转录因子。此外,MTP受常量营养素、激素和其他因素的调节。本文将阐述MTP受到调节的多种方式,并提出降低MTP水平而非抑制它可能是降低血脂的一种选择这一观点。