Abstract: Caffeic acid phenethyl ester (CAPE), a natural polyphenol derived from propolis, has a good regulatory effect on lipid metabolism, but its molecular mechanism is not clear. In the present study, the ameliorative effect of CAPE on lipid metabolism in oleic acid-induced HepG2 human liver cancer cells and its mechanism at the cellular level were investigated. The results showed that compared with the high fat group, lipid accumulation in the cells was significantly improved after CAPE intervention, and a total of 3 270 differentially expressed genes (DEGs) were selected at the transcriptomic level; 1 351 of them were up-regulated and the rest were down-regulated. The functional annotation analysis using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database showed that the DEGs caused by CAPE intervention were significantly annotated to lipid metabolism-related pathways. The KEGG signaling pathway enrichment analysis showed that the HIF-1α pathway and the fatty acid catabolism pathway were significantly enriched. The expression levels of gene HIF-1α, PPARα, CPT1A and FABP5 were 1.326, 1.661, 2.039 and 2.598 times higher in the CAPE group than the high fat group. It is suggested that CAPE can improve lipid metabolism disorder in oleic acid-induced cells possibly by reducing oxidative stress and regulating the PPARα and fatty acid oxidative catabolic pathways. This study provides a theoretical reference for future research on the molecular mechanism of lipid metabolism regulation by CAPE and the regulation of lipid metabolism disorder induced by a high-fat diet.

Key words: caffeic acid phenethyl ester; HepG2 cells; lipid metabolism; transcriptome; signaling pathway