ERR gamma directs and maintains the transition to oxidative metabolism in the postnatal heart

William A. Alaynick, Richard P. Kondo, Wen Xie, Weimin He, Catherine R. Dufour, Michael Downes, Johan W. Jonker, Wayne Giles, Robert K. Naviaux, Vincent Giguere, Ronald M. Evans*

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

217 Citaten (Scopus)

Samenvatting

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.

Originele taal-2English
Pagina's (van-tot)13-24
Aantal pagina's12
TijdschriftCell metabolism
Volume6
Nummer van het tijdschrift1
DOI's
StatusPublished - jul-2007
Extern gepubliceerdJa

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