CD36促进脂肪酸跨膜转运机制的研究

脂肪酸是机体必需的营养物质之一，广泛参与了多种重要的细胞功能。脂肪酸吸收，即其穿过细胞质膜进入细胞的过程，是脂肪酸代谢的第一步，是脂肪酸代谢的关键调控步骤。尽管如此，脂肪酸吸收机制的研究目前并不清楚。清道夫受体CD36是也被称为脂肪酸转位酶，能够促进细胞对脂肪酸的吸收。我们前期研究发现，CD36能够在脂肪酸刺激的情况下发生依赖于caveolin1的内吞，从脂肪细胞的细胞质膜转移到脂滴表面。鉴于长链脂肪酸是CD36的主要配体之一，我们推测脂肪酸介导的CD36内吞是一个配体介导的受体内吞过程，是CD36促进脂肪酸吸收的方式。而CD36往脂滴的迁移过程则将脂肪酸的吸收与酯化偶联到一起，从而实现细胞对脂肪酸的高效快速利用。我们将进一步明确D36内吞的具体过程，鉴定此过程所需的信号通路和重要蛋白质，证明CD36在脂肪酸吸收与酯化偶联中的作用，并最终阐明CD36通过内吞促进脂肪酸吸收的生理意义。

Long-chain fatty acids are important dietary nutrients and are involved in multiple cellular pathways and functions. Fatty acid uptake is the transport of fatty acids across the plasma membrane, and it is the first step for fatty acid utilization and also a key regulatory point in fatty acid metabolism; however, it remains largely unknown how fatty acids are transported across the plasma membrane. Here, our preliminary data show that oleic acid induces an endocytosis process of CD36 from plasma membrane to lipid droplets of 3T3-L1 adipocytes. Considering that long-chain fatty acids are ligands of CD36, we hypothesize that the endocytosis of CD36 induced by long-chain fatty acids is a ligand-induced process of receptor endocytosis, and that this might be the manner of how CD36 transport fatty acids from the extracellular matrix. Furthermore, the translocation of CD36 to lipid droplets might couple fatty acid uptake and esterification to ensure efficient utilization of fatty acids. We will therefore figure out the detailed process of the translocation of CD36, identify the signaling pathway and key molecules, prove the essential roles of CD36 in coupling fatty acid uptake and esterification, and uncover the physiological relevance of this process.