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脂肪细胞RNA结合蛋白CELF1通过稳定Dio2mRNA促进白脂肪的化

Ting Zeng¹, Liuling Xiao¹, Jiajie Li²

¹Department of Endocrinology, The First Affiliated Hospital, School of Basic Medicine, Chongqing Medical University, Chongqing, China.

Nature communications

|August 11, 2025

概括

CUG-BP Elav-like家族成员1 (CELF1) 是一种关键的RNA结合蛋白,促进白脂肪的结合和能量消耗. 肥胖症中CELF1的降低表明它是代谢疾病的治疗点.

科学领域:

代谢调节代谢调节代谢调节
脂肪细胞生物学脂肪细胞生物学
转录后控制转录后控制

背景情况:

RNA结合蛋白 (RBPs) 影响脂肪细胞的发育,但它们在白脂肪中扮演的角色尚不清楚.
白色脂肪组织 (WAT) 色对于能量消耗和对抗肥胖至关重要.
了解热生成中的RBPs可以揭示新的治疗点.

研究的目的:

确定关键的RBP调节白色脂肪组织的白色化.
阐明RBPs控制热生成的分子机制.
评估已识别的RBP在代谢性疾病中的治疗潜力.

主要方法:

鉴定CELF1作为关键的RBP在冷诱导的部WAT.
对脂肪细胞特异性Celf1缺陷对发热基因表达和能量消耗的影响的分析.
研究CELF1的机制,包括Dio2mRNA稳定性和局部三甲状腺素 (T3) 生产.
人体中CELF1表达与肥胖和体重指数 (BMI) 的相关性.
关于CELF1在色脂肪细胞激活和线粒体呼吸中的作用的体外研究.
评估Celf1过度表达在改善饮食引起的肥胖和代谢功能障碍.

主要成果:

已确定CELF1为一个关键的RBP,促进白色脂肪增生和热生成.
脂肪细胞特异性Celf1缺陷会损害寒冷引起的能量消耗.
CELF1稳定了Dio2mRNA,增强了局部T3的产生.
在肥胖症中,CELF1的表达减少,与BMI负相关.
CELF1增强了色脂肪细胞激活和线粒体呼吸.
过度表达CELF1可以改善代谢功能障碍,缓解饮食引起的肥胖.

结论:

CELF1是热生成和能量消耗的关键转录后调节器.
CELF1在代谢应激反应中起着生理作用.
CELF1代表了肥胖和相关代谢疾病的潜在治疗标.

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