该TBLR1/TBL1共因子复合体作为转录检查点在棕色脂肪组织对长时间暴露于寒冷的反应
Sahika Cingir Köker1,2,3,4, Foivos-Filippos Tsokanos1,2,3,4, Rabih El-Merahbi1,2,3,4
1Institute for Diabetes and Cancer (IDC), Helmholtz Center Munich (HMGU), Neuherberg, Germany.
概括
TBLR1/TBL1复合体对于棕色脂肪热生成至关重要. 它的删除会损害能量消耗和寒冷适应,突出其在代谢调节中的作用.
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
- 热生成是一种热生成.
背景情况:
- 棕色脂肪组织 (BAT) 对于热生成至关重要,需要NCOR/HDAC3核心压缩复合体.
- 该综合体包括TBL1和TBLR1蛋白质,其在BAT中的作用尚不清楚.
- 以前的研究表明,TBL1/TBLR1对其他组织的影响脂解.
研究的目的:
- 调查TBL1和TBLR1在棕色脂肪细胞热生成和BAT功能中的作用.
- 确定TBL1/TBLR1复杂删除对寒冷适应和能量恒温的影响.
主要方法:
- 在棕色脂肪细胞中单独删除TBLR1和TBL1/TBLR1.
- 在培养细胞中分析β-上腺素诱导的脂解和线粒体呼吸.
- 产生和分析UCP1-Cre介导的TBL1/TBLR1双淘汰赛小鼠.
主要成果:
- 单次删除TBLR1并没有影响感冒诱导的热生成.
- 结合TBL1/TBLR1丧失导致棕色脂肪细胞中的脂解和线粒体呼吸受损.
- 双击淘汰的小鼠在暴露在寒冷环境中显示出能耗降低,体温降低,BAT形态改变,并抑制PRDM16基因.
结论:
- TBLR1/TBL1复合体对于BAT适应寒冷和能量恒温是必不可少的.
- TBL1/TBLR1与HDAC3和PRDM16相互作用,这表明它在PRDM16介导的基因调节中发挥了作用.
- 这些发现揭示了核心压力复合体在代谢调节中的上下文依赖功能.
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