肝性雌激素受体α驱动了绝经后妇女的男性化,这些妇女患有与代谢功能障碍相关的性肝病
Clara Meda1, Valeria Benedusi2, Alessandro Cherubini3
1Department of Health Sciences, Università degli Studi di Milano, Milan, Italy.
JHEP reports : innovation in hepatology
|September 23, 2024
概括
更年期导致肝脏变化并增加MASLD的风险. 缺陷的雌激素受体α (ERα) 信号驱动肝脏的男性化,导致肥胖女性的MASLD,这表明ERα是治疗点.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 内分泌学 在内分泌学.
- 基因组学就是基因组学.
背景情况:
- 更年期诱导的卵巢功能丧失严重改变了新陈代谢,增加了与代谢功能障碍相关的脂肪性肝病 (MASLD) 的风险.
- 雌激素受体α (ERα) 是女性肝功能的关键,但其在绝经后MASLD发展中的作用尚不清楚.
研究的目的:
- 调查肝脏ERα信号对雌激素耗尽后MASLD发展的特定贡献.
- 为了确定是否受损的ERα信号驱动肝脏转录组男性化和小鼠和人类的MASLD.
主要方法:
- 来自假操作和卵巢切除 (OVX) 控制和肝脏ERα淘汰赛 (LERKO) 的雌性小鼠的肝脏转录组的RNA测序 (RNA-Seq) 分析.
- 来自一群肥胖个体的肝脏样本的分析,以评估翻译相关性.
主要成果:
- 卵巢切除在对照小鼠中诱导了显著的基因表达变化,但在LERKO小鼠中较少,证实了肝脏ERα在代谢重编程中的作用.
- 雌激素枯竭导致控制雌性肝脏的男性偏向基因的诱导,表明肝脏的男性化.
- 在患有MASLD的肥胖女性中,特别是在老年女性中,观察到类似向男性类肝脏转录组的类似转变.
结论:
- 肝脏ERα对于经过绝经后的肝脏转录组男性化中介至关重要.
- 向肝脏ERα可能提供一种针对性别的治疗策略,用于预防绝经后妇女的MASLD.
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