ERRγ directs and maintains the transition to oxidative metabolism in the postnatal heart

被引:266
作者
Alaynick, William A.
Kondo, Richard P.
Xie, Wen
He, Weimin
Dufour, Catherine R.
Downes, Michael
Jonker, Johan W.
Giles, Wayne
Naviaux, Robert K.
Giguere, Vincent
Evans, Ronald M. [1 ]
机构
[1] Salk Inst Biol Studies, Howard Hughes Med Inst, La Jolla, CA 92037 USA
[2] Salk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA
[3] Univ Calif San Diego, Program Biomed Sci, La Jolla, CA 92037 USA
[4] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92037 USA
[5] Univ Calif San Diego, Dept Med, La Jolla, CA 92037 USA
[6] Univ Pittsburgh, Ctr Pharmacogenet, Sch Pharm, Pittsburgh, PA 15213 USA
[7] Texas A&M Univ, Inst Biosci & Technol, Houston, TX 77030 USA
[8] McGill Univ, Mol Oncol Grp, Ctr Hlth, Montreal, PQ H3A 1A1, Canada
[9] Univ Calif San Diego, Sch Med, Mitochondrial & Metab Dis Ctr, San Diego, CA 92103 USA
关键词
RECEPTOR-ALPHA; PPAR-GAMMA; GENE-EXPRESSION; COACTIVATOR-1-ALPHA PGC-1-ALPHA; CARDIAC-HYPERTROPHY; FATTY-ACID; TRANSCRIPTION; CARDIOMYOPATHY; IDENTIFICATION; ACTIVATION;
D O I
10.1016/j.cmet.2007.06.007
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
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 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.
引用
收藏
页码:13 / 24
页数:12
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