Tran Tu T, Huang Wei-Jan, Lin Heng, Chen Hsi-Hsien
International Ph.D. Program in Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.
Department of Internal Medicine, Thai Nguyen University of Medicine and Pharmacy, Thai Nguyen 241-17, Vietnam.
Biomedicines. 2023 May 23;11(6):1509. doi: 10.3390/biomedicines11061509.
Obesity is an emerging concern globally with increasing prevalence. Obesity is associated with many diseases, such as cardiovascular disease, dyslipidemia, and cancer. Thus, effective new antiobesity drugs should be urgently developed. We synthesized SW20.1, a compound that induces activating transcription factor 3 (ATF3) expression. The results of Oil Red O staining and quantitative real-time polymerase chain reaction revealed that SW20.1 was more effective in reducing lipid accumulation in 3T3-L1 preadipocytes than the previously synthesized ST32db, and that it inhibited the expression of the genes involved in adipogenesis and lipogenesis. A chromatin immunoprecipitation assay indicated that SW20.1 inhibited adipogenesis and lipogenesis by binding to the upstream promoter region of resistin at two sites (-2861/-2854 and -241/-234). In mice, the intraperitoneal administration of SW20.1 reduced body weight, white adipocyte weight in different regions, serum cholesterol levels, adipogenesis-related gene expression, hepatic steatosis, and serum resistin levels. Overall, SW20.1 exerts antiobesity effects by inhibiting resistin through the ATF3 pathway. Our study results indicate that SW20.1 is a promising therapeutic drug for diet-induced obesity.
肥胖是一个在全球范围内日益受到关注且患病率不断上升的问题。肥胖与许多疾病相关，如心血管疾病、血脂异常和癌症。因此，迫切需要研发有效的新型抗肥胖药物。我们合成了SW20.1，一种能诱导激活转录因子3（ATF3）表达的化合物。油红O染色和定量实时聚合酶链反应结果显示，SW20.1在减少3T3-L1前脂肪细胞脂质积累方面比先前合成的ST32db更有效，并且它抑制了参与脂肪生成和脂质生成的基因表达。染色质免疫沉淀试验表明，SW20.1通过在两个位点（-2861/-2854和-241/-234）与抵抗素上游启动子区域结合来抑制脂肪生成和脂质生成。在小鼠中，腹腔注射SW20.1可降低体重、不同区域白色脂肪细胞重量、血清胆固醇水平、脂肪生成相关基因表达、肝脂肪变性和血清抵抗素水平。总体而言，SW20.1通过ATF3途径抑制抵抗素发挥抗肥胖作用。我们的研究结果表明，SW20.1是一种有前景的治疗饮食诱导性肥胖的药物。
