清华大学生物科学与技术系蛋白质科学教育部重点实验室，第四军医大附属西京医院病理学系，加拿大渥太华大学生物化学微生物和免疫学系的研究者在最新一期的Cell Metabolism上。
血液中高水平的三酰基甘油和胆固醇被认为是可能诱发肥胖，糖尿病和动脉粥样化的标志。肝脏分泌的极低密度脂蛋白（又称前β-脂蛋白，very-low density lipoproteins，简称VLDLs）在维持血液中三酰基甘油和胆固醇的水平方面起关键的作用，VLDLs能将三酰基甘油和胆固醇包裹起来形成微粒，从肝脏转运到其他组织做能量储备。
李蓬教授研究小组的工作者在本篇文章中主要破解了VLDLs如何在肝脏中包裹装配三酰基甘油和胆固醇的机制。
在棕色脂肪组织，肝脏和肾脏中发现有高水平的DFF45-like effector（DFF45样效应子b蛋白，简称cideb），cideb是在细胞凋亡的过程中诱导分泌的一种蛋白。Cideb具有调控脂质代谢的作用，然而，cideb调控脂质代谢的机制一直没有彻底弄清楚。Cideb如何与VLDLs相互作用也未有定论。
李蓬研究小组发现肝脏cideb缺乏活性（突变）的小鼠含有高水平的三酰基甘油量，而VLDls的分泌量却很低。此外，cideb被发现主要存在于脂质滴和内质网中，三酰基甘油主要在脂质滴和内质网中合成，VLDL也在其中合成。深入的研究发现在突变的小鼠体内载脂蛋白B是与cideb相互作用的蛋白，研究发现突变小鼠只有在cideb的载脂蛋白B和脂质滴结合域修复后才能恢复VLD的分泌。
这些研究结果表明，VLDL包裹三酰基甘油是在cideb的介导下完成的，研究小组认为cideb可能作为一个重要的治疗靶位，用于控制三酰基甘油和胆固醇水平。（生物谷Bioon.com）
生物谷推荐原始出处：
Cell Metabolism,4 February 2009 doi:10.1016/j.cmet.2008.12.013
Cideb, an ER- and Lipid Droplet-Associated Protein,Mediates VLDL Lipidation and Maturation byInteracting with Apolipoprotein B
Jing Ye1,2,John Zhong Li1,4,Yang Liu1,4,Xuanhe Li1,Tianshu Yang1,Xiaodong Ma1,Qing Li2,Zemin Yao3andPeng Li1,,
1 Protein Science Laboratory of Ministry of Education, Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing, China
2 Department of Pathology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China
3 Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada
4 These authors contributed equally to this work
Summary
Secretion of triacylglycerol-enriched very-low-density lipoproteins (VLDLs) from the liver is vital for maintaining plasma lipid homeostasis. However, the process of VLDL assembly and lipidation is not well characterized. Here, we observed that liver of Cideb null mice had higher levels of triacylglycerols accompanied bylow level of VLDL secretion. Furthermore, VLDL particles secreted from hepatocytes of Cideb null mice have low levels of triacylglycerols but normal levels of apoB. We also observed that Cideb is localized to endoplasmic reticulum and lipid droplets. Importantly, we have identified apoB as a Cideb-interacting protein. By infecting adenoviruses expressing various Cideb truncations into hepatocytes of Cideb null mice, we found that Cideb requires both its apoB-binding and lipid droplet association domains to restore the secretion of triacylglycerol-enriched VLDL particles. Our data suggest that Cideb promotes the formation of triacylglycerol-enriched VLDL particles and provides a molecular insight into VLDL lipidation and maturation in hepatocytes.
