脂肪酸转运蛋白CD36对骨骼肌细胞摄取脂肪酸具有重要的促进和调控功能。但过量的脂肪酸供应会导致CD36在细胞膜上长期驻留，使细胞对脂肪酸的摄取增加，最终引发胰岛素抵抗。但是脂肪酸诱导CD36转位的机制还不清楚。我们的研究揭示，脂肪酸在尚未引起肌细胞胰岛素抵抗时就可激活蛋白激酶Czeta（PKCzeta）、增加CD36在细胞膜上的分布，而PKCzeta活性被抑制后，细胞膜上的CD36明显减少。由此我们推测脂肪酸可能通过激活PKCzeta来促进CD36向细胞膜迁移，导致细胞对脂肪酸的过量摄取。本课题将以高脂饮食喂养的SD大鼠和棕榈酸诱导的L6骨骼肌细胞为模型，探讨在高脂条件下，骨骼肌细胞中PKCzeta调控CD36转位的分子机制及其与胰岛素抵抗的关系。本课题的实施有助于我们进一步了解血脂异常导致胰岛素抵抗的发病机理，并可为药物开发与干涉治疗提供有价值的靶点。

Fatty acid transporter CD36 plays key roles in facilitating and regulating fatty acid uptake in skeletal muscle cells. However, the permanent plasma membrane (PM) retention of CD36 in response to fatty acid oversupply may promote fatty acid uptake, which closely relates to insulin resistance. The mechanism of the CD36 translocation elicited by fatty acid still remains unclear. Our previous study revealed that both PKCzeta activity and cell surface CD36 increased upon fatty acid stimulation at the early stage when insulin resistance did not occur yet. Furthermore, the distribution of CD36 on PM deceased significantly when PKCzeta activation was inhibited. We therefore speculate that fatty acid may increase PM CD36 and enhance fatty acid uptake via PKCzeta activation. This proposed project aims to use high fat diet-fed SD rats and palmitate-induced L6 skeletal muscle cells as models to investigate the molecular mechanism of PKCzeta in regulating CD36 distribution and its relationship with insulin resistance during fatty acid stimulation. The implementation of the work may not only help us to further understand the pathogenesis of insulin resistance caused by dyslipidemia, but also provide promising therapeutic targets for drug development and intervention.