Holloway Graham P
Department of Human Health & Nutritional Sciences, University of Guelph, Guelph, ON N1G 2W1, Canada.
Appl Physiol Nutr Metab. 2009 Jun;34(3):440-6. doi: 10.1139/H09-028.
Fatty acid translocase (FAT/CD36) represents a novel flexible regulatory system, influencing rates of mitochondrial fatty acid metabolism in both human and rodent skeletal muscle. During exercise, the subcellular redistribution of FAT/CD36 provides a mechanism to increase not only plasma membrane fatty acid transport, but also mitochondrial fatty acid oxidation. This FAT/CD36-mediated coordination of long chain fatty acid (LCFA) transport and oxidation is an intriguing model in the context of insulin resistance. It was believed for almost a decade that reductions in fatty acid oxidation increased intramuscular lipids, thereby contributing to insulin resistance. A reduction in mitochondrial content may reduce the capacity of skeletal muscle LCFA oxidation; however, work from my laboratory has shown that, in some insulin-resistant muscles, mitochondrial content and fatty acid oxidation are both increased, yet these muscles accumulate lipids because of a considerably greater increase in fatty acid transport. Therefore, an alternative model is being considered, in which the balance between LCFA uptake and oxidation is a determining factor in the development of insulin resistance. A permanent redistribution of the LCFA transport protein FAT/CD36 to the sarcolemmal has been consistently found, which results in an increased rate of LCFA transport. This work suggests that the accumulation of skeletal muscle lipids, regardless of changes in mitochondria, is attributable to an increased rate of LCFA transport that exceeds the capacity for oxidation.
脂肪酸转运蛋白（FAT/CD36）代表一种新型的灵活调节系统，影响人和啮齿动物骨骼肌中线粒体脂肪酸代谢的速率。运动期间，FAT/CD36的亚细胞重新分布提供了一种机制，不仅可增加质膜脂肪酸转运，还能增加线粒体脂肪酸氧化。在胰岛素抵抗的背景下，这种由FAT/CD36介导的长链脂肪酸（LCFA）转运与氧化的协调是一个引人关注的模型。近十年来，人们一直认为脂肪酸氧化减少会增加肌肉内脂质，从而导致胰岛素抵抗。线粒体含量的减少可能会降低骨骼肌LCFA氧化的能力；然而，我实验室的研究表明，在一些胰岛素抵抗的肌肉中，线粒体含量和脂肪酸氧化均增加，但这些肌肉仍会积累脂质，原因是脂肪酸转运的增加幅度要大得多。因此，正在考虑一种替代模型，即LCFA摄取与氧化之间的平衡是胰岛素抵抗发生发展的决定性因素。人们一直发现LCFA转运蛋白FAT/CD36持续向肌膜永久性重新分布，这导致LCFA转运速率增加。这项研究表明，无论线粒体有无变化，骨骼肌脂质的积累都归因于LCFA转运速率的增加超过了氧化能力。
