Abstract
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.
Highlights
Caveolae, plasma membrane invaginations, plays a specific role in maintaining cellular cholesterol transportation and energy balance
In the plasma biochemical analysis, total cholesterol (TC), TG, low-density lipoprotein cholesterol (LDL-C), and high density lipoprotein (HDL)-C levels in the HFD group were significantly higher than in SD group, but significant difference was observed between HFD group and HFD with RSV group
To determine the activation of phosphoinositide 3-kinases (PI3Ks)/PKD1/Akt pathway, we examined the levels of phosphoPI3K, phospho-PKD1, and phospho-Akt by western blotting using phospho-specific antibodies
Summary
Plasma membrane invaginations, plays a specific role in maintaining cellular cholesterol transportation and energy balance. Caveolin-1 (Cav-1) is an integral membrane protein and the main structural protein of caveolae in nonmuscle cells. It has been reported that Cav-1 is important in the maintenance of hepatic lipid homeostasis[1]. Previous studies have extensively demonstrated that Cav-1 and caveolae contribute to regulate the hepatic energy metabolism by fatty acid oxidation [1,2].
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