在肝细胞巨中,ATF3介导的代谢重编程协调了与代谢功能障碍相关的脂肪肝炎
Shuwei Hu1,2, Rui Li3, Dongxu Gong3
1Key Laboratory of Metabolism and Molecular Medicine of the Ministry of Education, Department of Pathology of School of Basic Medical Sciences, Frontier Innovation Center, Fudan University, Shanghai 200032, China.
Science advances
|July 24, 2024
概括
巨细胞中的Atf3调节葡萄糖 - 脂肪酸循环,防止与代谢功能障碍相关的脂肪肝炎 (MASH). 向巨细胞Atf3或Rbp4为MASH提供了一个潜在的治疗策略.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 免疫学 免疫学 免疫学
- 代谢疾病 代谢疾病
背景情况:
- 代谢功能障碍相关的脂肪肝炎 (MASH) 涉及复杂的肝细胞相互作用.
- 巨细胞在MASH的发病过程中起着至关重要的作用.
研究的目的:
- 调查Atf3在MASH中葡萄糖-脂肪酸循环的巨介导调节中的作用.
- 探索Atf3对肝细胞肥胖症和肝星细胞纤维化的影响.
主要方法:
- 使用了MASH (西方饮食养小鼠) 的小鼠模型.
- 在巨细胞中操纵Atf3表达 (过度表达和切除).
- 研究了涉及FoxO1,Cd36和Rbp4.4的分子机制.
主要成果:
- 巨细胞Atf3过度表达保护了MASH的发展;Atf3剥离加剧了MASH.
- Atf3通过调节FoxO1和Cd36.3来增强脂肪酸的氧化作用.
- 大细胞Atf3通过Rbp4.4减少肝细胞脂质生成和HSC激活.
- 抗Rbp4疗法在Atf3缺乏的小鼠中减轻了MASH的进展.
结论:
- 在巨细胞中,Atf3充当葡萄糖-脂肪酸循环的关键调节者.
- 向巨细胞Atf3或Rbp4为MASH提供了一个有希望的治疗途径.
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