基脱乙酶3 准备棕色脂肪组织应对急热性挑战
Matthew J Emmett1,2, Hee-Woong Lim1,3, Jennifer Jager1,2
1Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
素脱酶3 (HDAC3) 对于棕色脂肪组织热生成至关重要. 失去HDAC3会损害产生热量的能力,导致低温和减少UCP1的表达.
科学领域:
- 代谢生理学
- 分子生物学
- 表观遗传学
背景情况:
- 棕色脂肪组织 (BAT) 产生热量以防止低温并对抗代谢疾病.
- 在暴露于寒冷之前,规范BAT热生成能力的精确转录机制尚不清楚.
研究的目的:
- 调查素脱乙酶3 (HDAC3) 在调节热生成能力方面的作用.
- 阐明HDAC3影响BAT功能的分子机制.
主要方法:
- 使用棕色脂肪组织特异性HDAC3遗传切除的小鼠模型.
- 评估了热生成能力,UCP1表达,线粒体呼吸和基因转录.
- 研究了HDAC3,PGC-1α和ERRα之间的相互作用.
主要成果:
- 在BAT中缺乏HDAC3的小鼠在暴露于寒冷时出现严重的低温和死亡.
- 缺少HDAC3导致UCP1的几乎完全丧失和线粒体氧化化基因的下调.
- HDAC3作为ERRα联合激活剂,对Ucp1,Ppargc1a和氧化化基因的基底转录至关重要,独立于上腺刺激.
结论:
- 在BAT中建立基底热生成转录程序时,HDAC3是不可或缺的.
- HDAC3通过脱乙PGC-1α和协同激活ERRα来启动快速热生成的BAT,确保在寒冷挑战之前的热生成能力.
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