肝脏时钟调节白色脂肪组织中的昼夜节律
Ivan Vlassakev1, Christina Savva1, Gianluca Renzi2
1Department of Physiology and Pharmacology, C3, Karolinska Institutet, 171 77 Stockholm, Sweden; Department of Medicine (H7), Karolinska Institutet, Stockholm 141 86, Sweden.
Molecular metabolism
|September 14, 2025
概括
肝脏时钟调节白色脂肪组织 (WAT) 的昼夜节律,影响脂质代谢和脂肪生成. 这种跨组织协调突出了核心时钟系统作为代谢健康的治疗目标.
科学领域:
- 内分泌学 在内分泌学.
- 代谢过程中的代谢.
- 时间生物学 时间生物学
背景情况:
- 循环节律对代谢健康至关重要,但跨组织协调机制尚不清楚.
- 肝脏在调节周围昼夜节律中的作用,特别是在白脂肪组织 (WAT) 中,需要进一步研究.
研究的目的:
- 研究肝脏时钟在调节昼夜节律和WAT中的脂质代谢中的作用.
- 确定肝脏时钟协调WAT生理学的机制.
主要方法:
- 肝细胞特定的Bmal1淘汰赛小鼠模型.
- 具有功能时钟的小鼠模型仅限于肝细胞.
- 在WAT中分析基因表达,脂质代谢和分泌的蛋白质.
- 对心脏代谢风险相关性的人类队列数据分析.
主要成果:
- 肝脏的昼夜控制调节了WAT中的脂质代谢和脂肪生成 (Cebpa表达).
- 只有肝脏的时钟才能整合养线索来调节WAT昼夜基因表达.
- 分泌的蛋白质,包括14-3-3η (Ywhah),介导肝脏时钟对WAT脂肪细胞的影响.
- 人类数据将肝脏时钟控制基因与心脏代谢风险联系起来.
结论:
- 肝脏时钟在协调昼夜节律和WAT中的新陈代谢方面发挥着核心作用.
- 肝-脂肪组织轴是系统代谢调节的关键组成部分.
- 准核心时钟系统为心脏代谢疾病提供了潜在的治疗策略.
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