在棕色脂肪细胞中,RyR2的HuR依赖表达有助于介导的热生成
bioRxiv : the preprint server for biology
|November 1, 2024
概括
人类抗原R (HuR) 的RNA结合蛋白对棕色脂肪组织热生成至关重要. HuR通过稳定氨酸受体2 (RyR2) mRNA来控制循环,这对于产生热量至关重要.
科学领域:
- 分子生物学分子生物学
- 代谢过程中的代谢.
- 脂肪组织生物学 脂肪组织生物学
背景情况:
- 在脂肪组织中存在脱蛋白1 (UCP1) 独立的热生成.
- 通过sarco/endoplasmic reticulum ATPase (SERCA) 进行介导的热生成是一种这样的途径.
- 之前的研究表明,脂肪细胞特异性删除人类抗原R (HuR) 损害了热生成.
研究的目的:
- 定义棕色脂肪细胞中驱动的热生成的HuR依赖机制.
- 研究HuR在调节离子运输和棕色脂肪组织中产生热量的作用.
主要方法:
- 生成的棕色脂肪组织 (BAT) 特定的HuR删除 (BAT-HuR-/-) 小鼠.
- 评估了发热功能,基因表达 (RyR2,SERCA,UCP1) 和细胞质水平 (Fluo-4染料).
- 利用ERtherm AC光进行热生成评估和RNA免疫沉以研究HuR-RyR2 mRNA相互作用.
主要成果:
- BAT-HuR-/-小鼠表现出寒冷不耐受,但体重和代谢参数正常.
- 在BAT-HuR-/-小鼠的BAT中观察到氨酸受体2 (RyR2) 表达的减少.
- 在棕色脂肪细胞中,HuR删除/抑制使度增加和β-上腺体介导的热量产生.
- HuR直接结合并稳定RyR2mRNA,而RyR2稳定可以挽救HuR缺乏细胞中的热生成缺陷.
结论:
- HuR在棕色脂肪组织热生成中发挥着关键作用.
- 对RyR2表达的HuR依赖控制对于SR循环和热量产生至关重要.
- 准HuR-RyR2轴可能为代谢障碍提供治疗策略.
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