Chabowski Adrian, Górski Jan, Luiken Joost J F P, Glatz Jan F C, Bonen Arend
Department of Physiology, Medical University of Bialystok, 15-089 Bialystok, Poland.
Prostaglandins Leukot Essent Fatty Acids. 2007 Nov-Dec;77(5-6):345-53. doi: 10.1016/j.plefa.2007.10.017.
There is substantial molecular, biochemical and physiologic evidence that long-chain fatty acid transport involves a protein-mediated process. A number of fatty acid transport proteins have been identified, and for unknown reasons, some of these are coexpressed in the same tissues. In muscle and heart FAT/CD36 and FABPpm appear to be key transporters. Both proteins are regulated acutely (within minutes) and chronically (hours to days) by selected physiologic stimuli (insulin, AMP kinase activation). Acute regulation involves the translocation of FAT/CD36 by insulin, muscle contraction and AMP kinase activation, while FABPpm is induced to translocate by muscle contraction and AMP kinase activation, but not by insulin. Protein expression ofFAT/CD36 and FABPpm is regulated by prolonged AMP kinase activation (heart) or increased muscle contraction. Prolonged insulin exposure increases the expression of FAT/CD36 but not FABPpm. Trafficking of fatty acid transporters between an intracellular compartment(s) and the plasma membrane is altered in insulin-resistant skeletal muscle, as some FAT/CD36 is permanently relocated to plasma membrane, thereby contributing to insulin resistance due to the increased influx of fatty acids into muscle cells. Studies in FAT/CD36 null mice have revealed that this transporter is key to regulating the increase in the rate of fatty acid metabolism in heart and skeletal muscle. It appears based on a number of experiments that FAT/CD36 and FABPpm may collaborate to increase the rates of fatty acid transport, as these proteins co-immunoprecipitate.
有大量分子、生化和生理学证据表明,长链脂肪酸转运涉及蛋白质介导的过程。已经鉴定出多种脂肪酸转运蛋白,并且由于未知原因,其中一些在相同组织中共表达。在肌肉和心脏中,FAT/CD36和FABPpm似乎是关键转运蛋白。这两种蛋白都受到特定生理刺激(胰岛素、AMP激酶激活)的急性(数分钟内)和慢性(数小时至数天)调节。急性调节涉及胰岛素、肌肉收缩和AMP激酶激活导致的FAT/CD36转位,而FABPpm通过肌肉收缩和AMP激酶激活被诱导转位,但不受胰岛素诱导。FAT/CD36和FABPpm的蛋白表达受延长的AMP激酶激活(心脏)或增加的肌肉收缩调节。长期暴露于胰岛素会增加FAT/CD36的表达,但不会增加FABPpm的表达。在胰岛素抵抗的骨骼肌中,脂肪酸转运蛋白在细胞内区室和质膜之间的转运发生改变,因为一些FAT/CD36永久重新定位到质膜,从而由于脂肪酸流入肌肉细胞增加而导致胰岛素抵抗。对FAT/CD36基因敲除小鼠的研究表明,这种转运蛋白是调节心脏和骨骼肌中脂肪酸代谢速率增加的关键。基于多项实验,FAT/CD36和FABPpm似乎可能协同作用以提高脂肪酸转运速率,因为这些蛋白可共免疫沉淀。