Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China.
School of Medicine, Anhui University of Science and Technology, Huainan, China.
Med Chem. 2023;19(9):879-888. doi: 10.2174/1573406419666230330141501.
Our previously reported naphthofuran derivative BF4, identified as a potent silent information regulator 1 (SIRT1) activator, could alleviate high glucose stimulating apoptosis and inflammation response in human renal tubular epithelial (HK-2) cells.
In this study, the underlying effects of BF4 on lipid metabolism in 3T3-L1 adipocytes were investigated.
The effects of BF4 on pre-adipocyte differentiation and adipocyte lipolysis were studied using oil red O staining and quantitative glycerol and triglyceride content assay kits. Moreover, the molecular mechanism of BF4 on adipogenesis and lipid metabolism in 3T3-L1 adipocytes was investigated by real-time quantitative PCR and Western blotting analysis.
We found that compound BF4 significantly decreased adipogenesis and lipid accumulation and inhibited the differentiation of 3T3-L1 pre-adipocytes into adipocytes. Moreover, compound BF4 decreased the expressions of several key regulators in adipocyte differentiation, including C/EBPβ and PPARγ, and their downstream lipogenesis targets via the activation of the SIRT1/ AMPK pathway.
Our results demonstrated that the novel SIRT1 activator BF4 might be a potent candidate for regulating lipid metabolism.
我们之前报道的萘并呋喃衍生物 BF4 被鉴定为一种有效的沉默信息调节因子 1（SIRT1）激活剂，可减轻高葡萄糖刺激的人肾小管上皮细胞（HK-2）细胞凋亡和炎症反应。
本研究旨在研究 BF4 对 3T3-L1 脂肪细胞中脂质代谢的潜在影响。
采用油红 O 染色和定量甘油和三酸甘油酯含量试剂盒研究 BF4 对前脂肪细胞分化和脂肪细胞脂肪分解的影响。此外，通过实时定量 PCR 和 Western 印迹分析研究了 BF4 对 3T3-L1 脂肪细胞中成脂作用和脂质代谢的分子机制。
我们发现，化合物 BF4 可显著降低脂肪生成和脂质积累，并抑制 3T3-L1 前脂肪细胞向脂肪细胞的分化。此外，化合物 BF4 通过激活 SIRT1/AMPK 通路，降低了脂肪细胞分化中的几个关键调节因子的表达，包括 C/EBPβ 和 PPARγ 及其下游的脂肪生成靶标。
我们的结果表明，新型 SIRT1 激活剂 BF4 可能是调节脂质代谢的有效候选药物。
