Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke, D-14558 Nuthetal, Germany.
Biosci Rep. 2013 Feb 22;33(1):1-9. doi: 10.1042/BSR20120082.
LDs (lipid droplets) carrying TAG (triacylglycerol) and cholesteryl esters are emerging as dynamic cellular organelles that are generated in nearly every cell. They play a key role in lipid and membrane homoeostasis. Abnormal LD dynamics are associated with the pathophysiology of many metabolic diseases, such as obesity, diabetes, atherosclerosis, fatty liver and even cancer. Chylomicrons, stable droplets also consisting of TAG and cholesterol are generated in the intestinal epithelium to transport exogenous (dietary) lipids after meals from the small intestine to tissues for degradation. Defective chylomicron formation is responsible for inherited lipoprotein deficiencies, including abetalipoproteinaemia, hypobetalipoproteinaemia and chylomicron retention disease. These are disorders sharing characteristics such as fat malabsorption, low levels of circulating lipids and fat-soluble vitamins, failure to thrive in early childhood, ataxic neuropathy and visual impairment. Thus understanding the molecular mechanisms governing the dynamics of LDs and chylomicrons, namely, their biogenesis, growth, maintenance and degradation, will not only clarify their molecular role, but might also provide additional indications to treatment of metabolic diseases. In this review, we highlight the role of two small GTPases [ARFRP1 (ADP-ribosylation factor related protein 1) and ARL1 (ADP-ribosylation factor-like 1)] and their downstream targets acting on the trans-Golgi (Golgins and Rab proteins) on LD and chylomicron formation.
载有三酰甘油 (TAG) 和胆固醇酯的脂滴 (LDs) 正在成为新兴的动态细胞细胞器，几乎存在于每一种细胞中。它们在脂质和膜动态平衡中发挥着关键作用。异常的 LD 动力学与许多代谢疾病的病理生理学有关，如肥胖、糖尿病、动脉粥样硬化、脂肪肝，甚至癌症。乳糜微粒，也是由 TAG 和胆固醇组成的稳定液滴，在肠上皮细胞中生成，用于在饭后将外源性（饮食）脂质从小肠转运到组织进行降解。乳糜微粒形成缺陷是遗传性脂蛋白缺乏的原因，包括 abetalipoproteinemia、hypobetalipoproteinaemia 和乳糜微粒滞留病。这些疾病具有脂肪吸收不良、循环脂质和脂溶性维生素水平低、幼儿期生长不良、共济失调性神经病和视力障碍等共同特征。因此，了解控制 LD 和乳糜微粒动力学的分子机制，即它们的生物发生、生长、维持和降解，不仅将阐明其分子作用，而且可能为代谢疾病的治疗提供额外的依据。在这篇综述中，我们强调了两个小 GTPases [ARFRP1（ADP-ribosylation factor related protein 1）和 ARL1（ADP-ribosylation factor-like 1）]及其下游作用于反式高尔基体的靶标（Golgins 和 Rab 蛋白）在 LD 和乳糜微粒形成中的作用。
