Department of Gastroenterology, Minhang Hospital of Fudan University, 170 Shensong Road, Shanghai, 201100, China.
Department of Gastroenterology, Zhongshan Hospital of Fudan University, 180 Fenglin Road, Shanghai, 200032, China.
J Mol Histol. 2024 Oct;55(5):995-1007. doi: 10.1007/s10735-024-10246-w. Epub 2024 Aug 13.
Dendrobine (DDB), an alkaloid isolated from the Chinese herb Dendrobium, has antioxidant and anti-inflammatory effects; however, whether DDB reduces oleic acid (OA)-induced lipid accumulation remains unclear. OA-induced lipid accumulation model of HepG2 cells were treated with DDB. Cellular lipid deposition was assessed by Oil Red O (ORO) staining and triglyceride and total cholesterol detection. RNA-Sequencing (RNA-seq), biological function analysis, and transcription factor (TFs) prediction were combined to identify key TF in the DDB-treated OA model. Finally, the roles of FOS and METTL14 were examined using a DDB-induced lipid accumulation model. DDB inhibited OA-induced lipid accumulation. We identified 895 differentially expressed genes (DEGs) that were mainly enriched in various biological processes of lipid synthesis and transport. Four transcription factors (SOX9, MLXIPL, FOS, and JUN) associated with lipid metabolism and FOS levels in the OA-induced lipid accumulation model after DDB treatment had the greatest changes in expression change. Overexpression of FOS alleviates the inhibitory effect of DDB on OA-induced lipid accumulation. METTL14 is a target gene of FOS, and simultaneous interference with METTL14 in cells with high FOS expression restored the alleviating effect of DDB on lipid accumulation. DDB alleviated OA-induced lipid accumulation by inhibiting the FOS/METTL14 pathway.
石斛碱（Dendrobine，DDB）是从中国草药石斛中分离得到的一种生物碱，具有抗氧化和抗炎作用；然而，DDB 是否能减少油酸（Oleic acid，OA）诱导的脂质积累尚不清楚。用 DDB 处理 OA 诱导的 HepG2 细胞脂质积累模型。通过油红 O（Oil Red O，ORO）染色和三酰甘油（triglyceride，TG）和总胆固醇（total cholesterol，TC）检测评估细胞内脂质沉积。结合 RNA 测序（RNA-seq）、生物功能分析和转录因子（Transcription factor，TF）预测，鉴定 DDB 处理 OA 模型中的关键 TF。最后，使用 DDB 诱导的脂质积累模型研究 FOS 和 METTL14 的作用。DDB 抑制 OA 诱导的脂质积累。我们鉴定了 895 个差异表达基因（Differentially expressed genes，DEGs），这些基因主要富集在脂质合成和转运的各种生物学过程中。四个与脂质代谢相关的转录因子（SOX9、MLXIPL、FOS 和 JUN）在 DDB 处理 OA 诱导的脂质积累模型中，其表达变化最大。FOS 的过表达减轻了 DDB 对 OA 诱导的脂质积累的抑制作用。METTL14 是 FOS 的靶基因，在 FOS 表达较高的细胞中同时干扰 METTL14，恢复了 DDB 对脂质积累的缓解作用。DDB 通过抑制 FOS/METTL14 通路缓解 OA 诱导的脂质积累。
