通过高脂肪饮食对脂肪组织中雌激素受体的表观遗传编程 调节肥胖引起的炎症
Rui Wu1,2, Fenfen Li2, Shirong Wang2
1School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, P. R. China.
bioRxiv : the preprint server for biology
|July 16, 2025
概括
高脂肪饮食增加了雌激素受体α (Esr1) 促进体的DNA甲基化,恶化了脂肪炎症和胰岛素抵抗. 减少这种甲基化可以改善小鼠的代谢健康.
科学领域:
- 代谢性疾病是一种代谢性疾病.
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 肥胖研究的研究.
背景情况:
- 脂肪性炎症是与肥胖相关的代谢功能障碍的核心.
- 像DNA甲基化这样的表观遗传修饰将环境因素与疾病联系起来.
- 高脂肪饮食 (HFD) 动态改变白色脂肪组织 (WAT) 中的DNA甲基组.
研究的目的:
- 研究DNA甲基化在HFD诱导的脂肪炎症和胰岛素抵抗中的作用.
- 确定向雌激素受体α (Esr1) 促进剂甲基化的对代谢健康的影响.
主要方法:
- 减少了代表性双硫酸盐测序来分析小鼠WAT的DNA甲基组变化.
- 在脂肪细胞中对DNA甲基转移酶 (Dnmt1,Dnmt3a) 的遗传操纵.
- 通过CRISPR/RNA引导的系统,专门去甲基化WAT中的Esr1促进体.
主要成果:
- HFD增加了Esr1促进体的DNA甲基化,减少了Esr1的表达,增加了脂肪炎症.
- 脂肪细胞特异性Dnmt1缺乏改善了Esr1表达,减少了脂肪炎症,并在HFD下增强了胰岛素敏感性.
- 通过CRISPR向减少Esr1促进物甲基化,改善了HFD养小鼠的代谢参数.
结论:
- 在Esr1促进体的DNA甲基化是脂肪炎症的关键调节者.
- 向Esr1促进剂甲基化代表了对肥胖引起的胰岛素耐药性的潜在治疗策略.
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