赛尔图因6激活剂UBCS039通过肝X受体脱来改善肝脏脂质发生
Ye Eun Cho1, Yeonsoo Kim1, Heeseon Jo1
1College of Pharmacy and Research Institute for Drug Development, Pusan National University, Busan 46241, Republic of Korea.
International immunopharmacology
|November 20, 2025
概括
一种新的SIRT6激活剂,UBCS039,通过向LXR-SREBF1通路,有效地抑制肝脏脂肪生成和炎症. 这一发现为治疗脂肪性肝病提供了有前途的治疗策略.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 肝病学 肝病学是一种肝病学.
背景情况:
- 赛尔图因6 (SIRT6) 在通过转录因子,如肝X受体 (LXR) 和固醇调控元素结合转录因子1 (SREBF1) 等转录因子调节肝脏脂质发生方面发挥作用.
- 缺乏SIRT6激活剂的开发,以抑制脂质生成和治疗脂肪性肝病.
研究的目的:
- 研究选择性SIRT6激活剂UBCS039对肝细胞中脂质基因表达和炎症的影响.
- 探索UBCS039在非酒精性脂肪肝疾病 (NAFLD) 的治疗潜力.
主要方法:
- 对来自NAFLD患者的RNA测序数据集的分析.
- 在体外研究中,使用用LXR激抗剂,UBCS039和SIRT6敲击治疗的肝细胞.
- 在体内研究,使用小鼠模型的肝硬化症.
主要成果:
- UBCS039通过促进LXR脱乙烯化来抑制LXR诱导的脂质基因表达,包括SREBF1.
- UBCS039减轻了肝细胞中的脂质积累,并抑制了NF-κB p65表达,减少了炎症.
- 抑制SIRT6逆转了UBCS039的抑制作用,证实了涉及SIRT6激活的机制.
- 在小鼠模型中UBCS039减弱的肝肥胖症.
结论:
- 通过UBCS039对SIRT6的药理活性抑制肝脏脂肪生成和炎症.
- UBCS039证明了作为治疗性肝脏疾病的治疗剂的潜力.
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