Department of Clinical Nutrition, Kecheng People's Hospital, Quzhou, Zhejiang Province, China.
Department of Preventive Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
PLoS One. 2017 Dec 6;12(12):e0189156. doi: 10.1371/journal.pone.0189156. eCollection 2017.
Resveratrol (RSV), a natural polyphenol, has been reported to produce effect on genes transcription in lipid metabolism. In this study, we aim to explore the novel mechanisms of RSV on the regulation of caveolin-1 (Cav-1) transcription. Via body weight, blood glucose, serum lipid, and liver pathology detection, we found that RSV decreased body weight, blood glucose and lipid accumulation in rats fed high-fat diet. Based on co-immunoprecipitation (Co-IP) and western blotting assay, we found that RSV up-regulated klf5 phosphorylation and decreased the interaction of klf5 with c-Myc, which were accompanied by down-regulation of Cav-1 expression in livers of rats fed with high-fat diet. Moreover, in HEK293 cells, we observed RSV enhanced klf5 phosphorylation and separated the interaction of klf5 with c-Myc through inhibiting the activation of PI3K/PKD1/Akt pathway, which maybe promoted c-Myc binding to the promoter to inhibit Cav-1 expression. The results of the present study demonstrated that RSV activated klf5 phosphorylation by inhibiting PI3K/PKD1/Akt pathway, and then attenuated the interaction of klf5 with c-Myc, subsequently probably promoted the c-Myc binding to the promoter to repress Cav-1 expression.
白藜芦醇（RSV）是一种天然多酚，据报道它可以影响脂质代谢基因的转录。在本研究中，我们旨在探索 RSV 调节小窝蛋白-1（Cav-1）转录的新机制。通过体重、血糖、血脂和肝组织病理学检测，我们发现 RSV 可降低高脂饮食喂养大鼠的体重、血糖和血脂蓄积。通过共免疫沉淀（Co-IP）和 Western blot 分析，我们发现 RSV 可增加 klf5 的磷酸化，减少 klf5 与 c-Myc 的相互作用，同时降低高脂饮食喂养大鼠肝脏中的 Cav-1 表达。此外，在 HEK293 细胞中，我们观察到 RSV 通过抑制 PI3K/PKD1/Akt 通路的激活增强了 klf5 的磷酸化并分离了 klf5 与 c-Myc 的相互作用，这可能促进 c-Myc 结合到启动子上抑制 Cav-1 的表达。本研究结果表明，RSV 通过抑制 PI3K/PKD1/Akt 通路激活 klf5 的磷酸化，然后减弱 klf5 与 c-Myc 的相互作用，进而可能促进 c-Myc 结合到启动子上抑制 Cav-1 的表达。
