通过向PPARγ对脂质代谢和Keap1-Nrf2途径激活巨细胞的调节影响NAFLD进展
Yu-Xin Chen1,2,3,4, Yan-Ping Wu1,2,3,4, Yi Zhang1,2,3,4
1Division of Gastroenterology and Hepatology, Shanghai, China.
Journal of gastroenterology and hepatology
|June 6, 2025
概括
在巨细胞中调节过氧体增殖器激活受体 (PPARγ) 影响脂质代谢,减少氧化应激,抑制炎症,为非酒精性脂肪肝疾病 (NAFLD) 提供潜在的治疗策略.
科学领域:
- 细胞生物学 细胞生物学
- 代谢疾病 代谢疾病
- 免疫学 免疫学 免疫学
背景情况:
- 脂质代谢重编程影响巨细胞的炎症和免疫功能.
- 巨PPARγ在脂质代谢和NAFLD中氧化应激中的特定作用尚未完全理解.
研究的目的:
- 研究调节巨细胞PPARγ表达对脂质代谢,氧化应激和炎症的影响.
- 评估巨PPARγ在非酒精性脂肪性肝病 (NAFLD) 的进展中的作用.
主要方法:
- 已建立的NAFLD巨细胞模型使用RAW264.7细胞,库弗弗细胞和暴露于和脂肪酸的骨髓衍生巨细胞.
- 利用PPARγ激动剂/对抗剂,基因淘汰和过度表达来调节巨细胞中的PPARγ.
- 创建了NAFLD小鼠模型并评估了脂质代谢,氧化应激和炎症 in vivo 和 in vitro.
主要成果:
- 在巨细胞中PPARγ的上调增强了脂肪酸氧化,减少了ROS的产生,并抑制了炎症.
- 观察到Keap1-Nrf2通路的PPARγ激活.
- 巨细胞特异性PPARγ淘汰在NAFLD小鼠中恶化了肝炎和损伤.
结论:
- 在巨细胞中调节PPARγ表达会影响脂质代谢,氧化应激和炎症.
- 准宏细胞特异性PPARγ活性为NAFLD提供了潜在的治疗途径.
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