Department of Pediatrics and Cell Biology, Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta, Canada.
Arterioscler Thromb Vasc Biol. 2012 May;32(5):1087-93. doi: 10.1161/ATVBAHA.111.241497.
Overproduction of apolipoprotein B (apoB)-containing lipoproteins by the liver and the intestine is 1 of the hallmarks of insulin resistance and type 2 diabetes and a well-established risk factor of cardiovascular disease. The assembly of apoB lipoproteins is regulated by the availability of lipids that form the neutral lipid core (triacylglycerol and cholesteryl ester) and the limiting lipoprotein monolayer (phospholipids and cholesterol). Although tremendous advances have been made over the past decade toward understanding neutral lipid and phospholipid biosynthesis and neutral lipid storage in cytosolic lipid droplets (LDs), little is known about the mechanisms that govern the transfer of lipids to the lumen of the endoplasmic reticulum for apoB lipidation. ApoB-synthesizing organs can deposit synthesized neutral lipids into at least 3 different types of LDs, each decorated with a subset of specific proteins: perilipin-decorated cytosolic LDs, and 2 types of LDs formed in the lumen of the endoplasmic reticulum, the secretion-destined LDs containing apoB, and resident lumenal LDs coated with microsomal triglyceride transfer protein and exchangeable apolipoproteins. This brief review will address the current knowledge of lumenal lipid metabolism in the context of apoB assembly and lipid storage.
肝脏和肠道中载脂蛋白 B（apoB）所含脂蛋白的过度生产是胰岛素抵抗和 2 型糖尿病的特征之一，也是心血管疾病的既定危险因素。apoB 脂蛋白的组装受形成中性脂质核心（甘油三酯和胆固醇酯）和限制脂蛋白单层（磷脂和胆固醇）的脂质可用性调节。尽管在过去十年中，人们在理解细胞质脂滴（LD）中的中性脂质和磷脂生物合成以及中性脂质储存方面取得了巨大进展，但对于控制脂质向内质网腔转移以进行 apoB 脂质化的机制知之甚少。合成 apoB 的器官可以将合成的中性脂质沉积到至少 3 种不同类型的 LD 中，每种 LD 都用特定蛋白质的子集进行修饰：围脂滴蛋白修饰的细胞质 LD，以及内质网腔中形成的 2 种 LD，含有 apoB 的分泌定向 LD 和涂有微粒体甘油三酯转移蛋白和可交换载脂蛋白的驻留腔 LD。这篇简短的综述将讨论 apoB 组装和脂质储存背景下内质网腔中脂质代谢的最新知识。
