腺酸合成酶1缺乏改善能量代谢,通过促进脂肪组织再化通过糖激酶上调调节脂肪组织再化
Jingjing Sun1, Miriayi Alimujiang1,2,3, Wenfei Li1
1Department of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|October 21, 2025
概括
腺酸合成酶1 (Adss1) 通过控制糖醇激酶 (Gk) 表达来调节脂肪组织代谢,与UCP1.1不同. 缺少Adss1会增加能量消耗,并对抗肥胖.
科学领域:
- 脂肪组织生物学 脂肪组织生物学
- 代谢调节 代谢调节 代谢调节
- 纯氨酸生物合成 纯氨酸生物合成
背景情况:
- purin代谢酶维持核酸池和细胞能量恒温.
- 热源性脂肪细胞中的解蛋白1 (UCP1) 活性受精氨酸核酸度的影响.
研究的目的:
- 调查腺酸盐合成酶1 (Adss1) 在调节 inguinal 白脂肪组织 (iWAT) 中代谢重塑中的作用.
- 阐明Adss1影响脂肪组织代谢的机制,独立于UCP1活动.
主要方法:
- 产生脂肪特异性的Adss1淘汰赛小鼠和双淘汰赛小鼠 (Adss1和Gk).
- 评估能量消耗,体重和代谢功能障碍.
- 分析糖醇激酶 (Gk) 表达,脂肪酸再化和iWAT棕色化.
- 研究Adss1与基因素脱乙酶3 (HDAC3) 的相互作用及其对Gk促进剂乙化的影响.
主要成果:
- 特定于脂肪的Adss1淘汰赛小鼠表现出增加的能量消耗,抵抗饮食诱导的肥胖,并改善了代谢功能障碍.
- 失去了Adss1调高了Gk表达,刺激了依赖糖的脂肪酸再化,并防止了脂毒性.
- 缺少Adss1促进了iWAT棕色化,这是一个依赖于Gk的过程.
- Adss1与HDAC3相互作用,降低了核HDAC3水平,并增加了Gk促销器中的素乙化,从而提高了Gk的表达.
结论:
- Adss1是iWAT中代谢重塑的关键调节者,通过一种涉及Gk上调的机制,与UCP1活动不同.
- 缺少Adss1促进iWAT色,并通过依赖Gk的途径增加能源消耗.
- Adss1与HDAC3的相互作用调节Gk表达,突出了脂肪生理学的新型调节轴.
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