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首页> 外文期刊>Cell metabolism >ERRgamma directs and maintains the transition to oxidative metabolism in the postnatal heart.
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ERRgamma directs and maintains the transition to oxidative metabolism in the postnatal heart.

机译:ERRgamma指导并维持产后心脏向氧化代谢的转变。

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摘要

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 ERRgamma 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 ERRgamma 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 ERRgamma in thestudy of cardiac hypertrophy and failure.
机译:出生时,心脏经历了关键的代谢转换,从胎儿生命中对碳水化合物的主要依赖转变为对产后氧化代谢的更大依赖。尽管诸如心力衰竭和心脏肥大之类的病理状况会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,但这仍然是整个生命中的主要代谢状态。 ERRgamma基因(Esrrg)的破坏在胎儿和出生后的小鼠心脏中高水平表达,阻止了这种转换,导致乳酸血症,心电图异常和生命的第一周死亡。基因组芯片上芯片和表达分析确定ERRgamma是协调出生后代谢转变的核编码线粒体遗传网络的直接和间接调节剂。这些发现揭示了心脏氧化代谢基因程序中一个意想不到且必不可少的分子遗传成分,并在心脏肥大和衰竭研究中突出了ERRgamma。

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