营养驱动的素乙化是能量储存和动员的基础
Linyun Chen1, Lingyan Zhu2, Huabing Xiao1
1Jiangxi Hypertension Research Institute, Nanchang, 330006, China; Department of Cardiovascular Medicine, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, China; Department of Endocrinology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, China.
代谢状态影响能量平衡的表观遗传修饰. 乙-A短链合成酶2 (ACSS2) 和BRD4是关键调节剂,为NAFLD等代谢性疾病提供潜在的治疗点.
科学领域:
- 代谢调节 代谢调节 代谢调节
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 分子生物学分子生物学
背景情况:
- 储能和动员能维持新陈代谢的平衡.
- 失衡会导致代谢功能障碍,但与表观遗传学的联系尚不清楚.
- 了解能量平衡的表观遗传控制至关重要.
研究的目的:
- 研究将新陈代谢状态与能量储存和动员联系起来的表观遗传机制.
- 澄清葡萄糖,体,ACSS2和BRD4在这个过程中的作用.
- 探索代谢性疾病的治疗潜力.
主要方法:
- 在过度养和禁食状态下研究了表观遗传修饰 (基因组乙化).
- 评估了乙-CoA短链合成酶2 (ACSS2) 和BRD4.4的参与.
- 使用高脂肪,原和禁食饮食的小鼠模型.
- 研究了BRD4抑制对非酒精性脂肪性肝病 (NAFLD) 和肝硬化症的影响.
主要成果:
- 在过度养中增加的葡萄糖通过ACSS2增强了基因素乙化,促进了脂质生成.
- 禁食时的体改变了组 histone 的乙化和基因表达,转向了代谢 (脂肪酸氧化).
- 在这两种状态中,BRD4对于识别基因素乙化和调节转录至关重要.
- 抑制BRD4可以缓解高脂肪饮食引起的NAFLD,但在禁食/代状态下会恶化肝肥.
结论:
- 能量储存/动员的表观遗传调节与体内可用的葡萄糖和有关.
- 在新陈代谢适应中,BRD4发挥着上下文依赖的作用.
- 准ACSS2通路可能为NAFLD等代谢性疾病提供新的治疗方法.
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