Laboratory of Clinical Pharmaceutics, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu, Japan.
Biomarker Laboratory, Research Institute for Production Development, Kyoto, Japan.
Biosci Biotechnol Biochem. 2022 May 24;86(6):747-754. doi: 10.1093/bbb/zbac043.
Royal jelly (RJ) intake has been reported to be effective for reducing serum lipids; however, the mechanism is not fully understood. Angiopoietin-like protein 8 (ANGPTL8), a secreted protein, plays a key role in lipid metabolism. In this study, we investigated the effects of specific fatty acids included in RJ (RJ fatty acids), such as 10-hydroxy-2-decenoic acid, 10-hydroxydecanoic acid, and sebacic acid (SA), on expression of ANGPTL8 in human hepatoma HepG2 cells. SA markedly reduced the expression of ANGPTL8. Reporter assay revealed that SA suppressed ANGPTL8 promoter activity. In addition, we identified a functional binding site of hepatocyte nuclear factor-4α (HNF4α), a liver-enriched transcription factor, in the ANGPTL8 promoter. SA reduced the levels of HNF4α protein and the binding of HNF4α to the ANGPTL8 promoter. Moreover, siRNA knockdown of HNF4α suppressed the expression of ANGTPL8 mRNA. Taken together, we conclude that SA downregulates ANGPTL8 expression via the decrease in HNF4α protein.
蜂王浆（RJ）的摄入已被报道可有效降低血清脂质；然而，其机制尚不完全清楚。血管生成素样蛋白 8（ANGPTL8）是一种分泌蛋白，在脂质代谢中发挥关键作用。在这项研究中，我们研究了 RJ 中所含的特定脂肪酸（RJ 脂肪酸），如 10-羟基-2-癸烯酸、10-羟基癸酸和癸二酸（SA），对人肝癌 HepG2 细胞中 ANGPTL8 表达的影响。SA 显著降低了 ANGPTL8 的表达。报告基因检测显示 SA 抑制了 ANGPTL8 启动子活性。此外，我们在 ANGPTL8 启动子中鉴定了一个功能性的肝富集转录因子肝细胞核因子 4α（HNF4α）结合位点。SA 降低了 HNF4α 蛋白水平和 HNF4α 与 ANGPTL8 启动子的结合。此外，siRNA 敲低 HNF4α 抑制了 ANGTPL8 mRNA 的表达。综上所述，我们得出结论，SA 通过降低 HNF4α 蛋白水平下调 ANGPTL8 的表达。
