Yang Yingkui, Chen Min, Loux Tara J, Harmon Carroll M
Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35205, USA.
Pediatr Surg Int. 2007 Jul;23(7):675-83. doi: 10.1007/s00383-007-1942-6. Epub 2007 May 22.
Defects in fatty acid translocase (FAT/CD36) have been identified as a major factor in insulin resistance and defective fatty acid and glucose metabolism. Therefore, understanding of the regulation of FAT/CD36 expression and function is important for a potential therapeutic target for type II diabetes. We differentiated 3T3-L1 preadipocytes into matured adipocytes and examined the roles of insulin and long chain fatty acids on FAT/CD36 expression and function. Our results indicate that FAT/CD36 mRNA expression was not detected at preadipocyte but was significantly increased at matured adipocyte. In fully differentiated 3T3-L1 adipocytes, insulin significantly increased FAT/CD36 mRNA and protein expression in a dose dependent manner. The free fatty acid stearic acid reduced FAT/CD36 mRNA expression while the non-metabolizable free fatty acid alpha-bromopalmitate (2-BP) significantly increased FAT/CD36 mRNA and protein expression. Isoproterenol, in contrast, dose-dependently reduced FAT/CD36 mRNA expression and increased free fatty acid release. Mechanism analysis indicated that the effect of insulin and 2-BP on the FAT/CD36 mRNA gene expression may be mediated through activation of PPAR-gamma, suggesting that FAT/CD36 may have important implications in the pathophysiology of defective fatty acid metabolism.
脂肪酸转位酶（FAT/CD36）缺陷已被确认为胰岛素抵抗以及脂肪酸和葡萄糖代谢缺陷的主要因素。因此，了解FAT/CD36表达和功能的调控对于II型糖尿病潜在治疗靶点而言非常重要。我们将3T3-L1前脂肪细胞分化为成熟脂肪细胞，并研究了胰岛素和长链脂肪酸对FAT/CD36表达和功能的作用。我们的结果表明，在前脂肪细胞中未检测到FAT/CD36 mRNA表达，但在成熟脂肪细胞中显著增加。在完全分化的3T3-L1脂肪细胞中，胰岛素以剂量依赖方式显著增加FAT/CD36 mRNA和蛋白质表达。游离脂肪酸硬脂酸降低了FAT/CD36 mRNA表达，而非代谢性游离脂肪酸α-溴棕榈酸酯（2-BP）显著增加了FAT/CD36 mRNA和蛋白质表达。相比之下，异丙肾上腺素剂量依赖性地降低FAT/CD36 mRNA表达并增加游离脂肪酸释放。机制分析表明，胰岛素和2-BP对FAT/CD36 mRNA基因表达的影响可能通过激活PPAR-γ介导，提示FAT/CD36可能在脂肪酸代谢缺陷的病理生理学中具有重要意义。
