通过PARP7感知NAD 调节体内脂肪组织中C/EBPβ-依赖的转录程序
bioRxiv : the preprint server for biology
|April 28, 2025
概括
聚 (ADP-ribose) 聚合酶7 (PARP7) 调节脂肪细胞形成 (脂肪生成) 和乳腺功能. 在PARP7中,PARP7是PARP7的一部分.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 脂肪生成,脂肪细胞形成的过程,对于代谢健康至关重要,涉及复杂的转录调节.
- 聚 (ADP-ribose) 聚合酶7 (PARP7) 是一种参与DNA修复和其他细胞过程的酶,但其在脂肪生成中的作用尚不清楚.
- 尼古丁胺胺单核酸 (NMN) 是NAD+的重要前体,对于细胞能量代谢至关重要,在母乳中发现.
研究的目的:
- 研究PARP7在调节C/EBPβ依赖的益基转录程序中的作用.
- 阐明PARP7控制脂肪生成和相关生理功能的分子机制.
- 检查PARP7对乳腺发育和牛奶成分的影响.
主要方法:
- 鉴定PARP7作为C/EBPβ依赖基因表达的调节者.
- 评估PARP7的催化活性及其通过核NAD+水平的调节.
- 分析PARP7与E3酶 (DTX2,RNF114) 的相互作用及其随处可见的降解.
- 在体内使用小鼠模型评估PARP7在脂肪生成和乳腺功能中的作用.
主要成果:
- PARP7是脂肪生成的关键调节者,作为C/EBPβ的联合激活剂,影响其基因组结合.
- PARP7的活动通过自动单一的ADP-ribosyl化 (自动MARylation) 通过核NAD+水平进行调节,影响其稳定性.
- 在小鼠中,PARP7的耗尽导致脂肪生成减少,乳腺发育受损,以及由于NAMPT表达减少而导致牛奶中的NMN水平降低.
结论:
- 通过调节C/EBPβ活性和NAD+代谢,PARP7在脂肪生成和围产期健康中发挥着关键作用.
- 这项研究揭示了一种新的调节途径,涉及PARP7,NAD+和E3链酶控制脂肪生成和乳腺功能.
- PARP7的功能扩展到调节NAMPT的表达,影响对后代营养至关重要的NMN水平.
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