The Transcriptional Corepressor RIP140 Regulates Oxidative Metabolism in Skeletal Muscle

Asha Seth, Jennifer H. Steel, Donna Nichol, Victoria Pocock, Kumaran Kuppusamy Mande, Asmaa Fritah, Margaret Mobberley, Timothy A. Ryder, Anthea Rowlerson, James Scott, Matti Poutanen, Roger White, Malcolm Parker*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    151 Scopus citations

    Abstract

    Nuclear receptor signaling plays an important role in energy metabolism. In this study we demonstrate that the nuclear receptor corepressor RIP140 is a key regulator of metabolism in skeletal muscle. RIP140 is expressed in a fiber type-specific manner, and manipulation of its levels in null, heterozygous, and transgenic mice demonstrate that low levels promote while increased expression suppresses the formation of oxidative fibers. Expression profiling reveals global changes in the expression of genes implicated in both myofiber phenotype and metabolic functions. Genes involved in fatty-acid oxidation, oxidative phosphorylation, and mitochondrial biogenesis are upregulated in the absence of RIP140. Analysis of cultured myofibers demonstrates that the changes in expression are intrinsic to muscle cells and that nuclear receptor-regulated genes are direct targets for repression by RIP140. Therefore RIP140 is an important signaling factor in the regulation of skeletal muscle function and physiology.

    Original languageEnglish (US)
    Pages (from-to)236-245
    Number of pages10
    JournalCell Metabolism
    Volume6
    Issue number3
    DOIs
    StatePublished - Sep 5 2007

    Keywords

    • DNA

    ASJC Scopus subject areas

    • Physiology
    • Molecular Biology
    • Cell Biology

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