Regulation of fatty acid transport and membrane transporters in health and disease
Regulation of fatty acid transport and membrane transporters in health and disease
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DOI：
10.1023/a:1020511125085
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发表时间：
2002-10-01
影响因子：
4.3
通讯作者：
Glatz, JFC
中科院分区：
文献类型：
--
作者：
Bonen, A;Luiken, JJFP;Glatz, JFC
长链脂肪酸跨质膜摄取部分地通过蛋白质介导的过程发生，该过程涉及许多被称为脂肪酸转运蛋白的脂肪酸结合蛋白。进一步理解脂肪酸转运的关键一步是发现从肌肉和心脏等组织中制备的巨大囊泡提供了测量脂肪酸摄取的合适系统。这些囊泡很大（直径10-15 μ m），完全右侧向外，并且在管腔中含有细胞溶质FABP，其充当脂肪酸汇，而吸收的脂肪酸没有一个被代谢或与质膜相关。关键的脂肪酸转运蛋白FAT/CD 36和FABPpm在肌肉和心脏中表达，并且它们的质膜含量与脂肪酸转运速率正相关。这些转运蛋白受到急性（几分钟内）和慢性（几天）的调节。例如，肌肉收缩和胰岛素都可以将FAT/CD 36从细胞内库转移到质膜，从而增加脂肪酸转运。对于肥胖症，脂肪酸转运增加，同时质膜FAT/CD 36（心脏、肌肉）和FABPpm（仅心脏）也随之增加，但这些转运蛋白的表达没有变化。沿着。后一种观察结果表明，一些脂肪酸转运蛋白被永久性地重新定位到质膜上。在其他研究中，脂肪酸转运速率似乎也以与葡萄糖转运相反的方式改变。由于脂质代谢紊乱似乎是一个重要的因素，导致一些常见的人类疾病，如糖尿病和肥胖症的病因，我们的证据表明，蛋白质介导的脂肪酸转运是脂质代谢的关键步骤允许推测，脂肪酸转运过程的故障可能是这些疾病的发病机制中的一个共同的关键因素。
Long chain fatty acid uptake across the plasma membrane occurs, in part, via a protein-mediated process involving a number of fatty acid binding proteins known as fatty acid transporters. A critical step in furthering the understandings of fatty acid transport was the discovery that giant vesicles, prepared from tissues such as muscle and heart, provided a suitable system for measuring fatty acid uptake. These vesicles are large (10-15 mum diameter), are oriented fully right side out, and contain cytosolic FABP in the lumen, which acts as a fatty acid sink, while none of the fatty acid taken up is metabolized or associated with the plasma membrane. The key fatty acid transporters FAT/CD36 and FABPpm are expressed in muscle and heart and their plasma membrane content is positively correlated with rates of fatty acid transport. These transporters are regulated acutely ( within minutes) and chronically ( days). For instance, both muscle contraction and insulin can translocate FAT/CD36 from an intracellular pool to the plasma membrane, thereby increasing fatty acid transport. With obesity, fatty acid transport is increased along with a concomitant increase in plasmalemmal FAT/CD36 ( heart, muscle) and FABPpm ( heart only), but without change in the expression of these transporters. This latter observation suggests that some of the fatty acid transporters are permanently relocated to the plasma membrane. In other studies it also appears that fatty acid transport rates are altered in a reciprocal manner to glucose transport. Since disorders in lipid metabolism appear to be an important factor contributing to the etiology of a number of common human diseases such as diabetes and obesity, our evidence that protein-mediated fatty acid transport is a key step in lipid metabolism allows the speculation that malfunctioning of the fatty acid transport process could be a common critical factor in the pathogenesis of these diseases.