激活转录因子3在代谢应激时调节肝脏的阿波利波蛋白A4
Jasmine Encarnacion1, Danielle M Smith2, Joseph Choi2
1Department of Physiology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
The Journal of biological chemistry
|March 30, 2025
概括
激活转录因子3 (Atf3) 和阿波利波蛋白A4 (ApoA4) 是响应代谢压力的肝脏关键蛋白质. 它们的调节对于维持葡萄脂平衡至关重要,特别是在禁食或特定饮食期间.
科学领域:
- 代谢调节 代谢调节 代谢调节
- 肝脏生理学 肝脏生理学
- 分子生物学分子生物学
背景情况:
- 肝脏是维持全身血糖脂质平衡的核心.
- 代谢失调会导致适应性和不适应性生理变化.
- 确定代谢应激反应的关键调节者至关重要.
研究的目的:
- 为了识别循环中的蛋白质,在响应肝脏特定的代谢压力因素时进行上调.
- 研究激活转录因子3 (Atf3) 在代谢应激中的作用.
- 阐明Atf3与肝脏中的阿波利波蛋白A4 (ApoA4) 之间的关系.
主要方法:
- 检查了卡尼丁棕基转移酶2 (Cpt2) 和酸盐碳化酶 (PC) 的肝脏特异性淘汰赛 (KO) 模型.
- 评估了禁食,高脂肪和性饮食对蛋白质表达的影响.
- 使用肝脏特异性Atf3过度表达和双KO小鼠模型 (Atf3,Cpt2).
主要成果:
- 在肝脏特异性KO模型中,Apolipoprotein A4 (ApoA4) 的升高调节,并在禁食/饮食中加剧.
- 激活转录因子3 (Atf3) 的表达与ApoA4.4同时增加.
- 肝脏特异性Atf3过度表达增加了ApoA4的表达,以一种取决于性别的方式.
- 为了诱导ApoA4mRNA,ApoA4蛋白和血清甘油三,需要Atf3.
结论:
- 肝脏Atf3在ApoA4.4的性别依赖调节中发挥着关键作用.
- Atf3和ApoA4是肝脏对体内代谢压力的反应的关键组成部分.
- 这些发现提供了对新陈代谢恒常的分子机制的洞察.
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