ERRγ directs and maintains the transition to oxidative metabolism in the postnatal heart
ERRγ directs and maintains the transition to oxidative metabolism in the postnatal heart
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DOI：
10.1016/j.cmet.2007.06.007
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发表时间：
2007-07-01
期刊：
影响因子：
29
通讯作者：
Evans, Ronald M.
中科院分区：
文献类型：
--
作者：
Alaynick, William A.;Kondo, Richard P.;Evans, Ronald M.
出生时，心脏经历了一个关键的代谢转换，从胎儿期主要依赖碳水化合物到出生后更依赖氧化代谢。这仍然是整个生命的主要代谢状态，虽然病理条件，如心力衰竭和心脏肥大重新激活胎儿遗传程序的组成部分，以增加碳水化合物的利用。ERR γ基因（Esrrg）在胎儿和出生后小鼠心脏中以高水平表达，其破坏阻断了这种转换，导致乳酸血症、心电图异常和生命第一周期间的死亡。基因组ChIP芯片和表达分析确定ERR γ作为核编码的线粒体遗传网络的直接和间接调节因子，该网络协调出生后的代谢转变。这些发现揭示了心脏中氧化代谢基因程序的一个意想不到的和必要的分子遗传组成部分，并突出了心脏肥大和衰竭研究中的ERR γ。
At birth, the heart undergoes a critical metabolic switch from a predominant dependence on carbohydrates during fetal life to a greater dependence on postnatal oxidative metabolism. This remains the principle metabolic state throughout life, although pathologic conditions such as heart failure and cardiac hypertrophy reactivate components of the fetal genetic program to increase carbohydrate utilization. Disruption of the ERR gamma gene (Esrrg), which is expressed at high levels in the fetal and postnatal mouse heart, blocks this switch, resulting in lactatemia, electrocardiographic abnormalities, and death during the first week of life. Genomic ChIP-on-chip and expression analysis identifies ERR gamma as both a direct and an indirect regulator of a nuclear-encoded mitochondrial genetic network that coordinates the postnatal metabolic transition. These findings reveal an unexpected and essential molecular genetic component of the oxidative metabolic gene program in the heart and highlight ERR gamma in the study of cardiac hypertrophy and failure.