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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / genetics
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Adaptor Proteins, Signal Transducing / metabolism*
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Animals
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Cadherins / genetics
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Cadherins / metabolism
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Cells, Cultured
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ERRalpha Estrogen-Related Receptor
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Energy Metabolism*
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Fatty Acid Binding Protein 3
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Fatty Acid-Binding Proteins / genetics
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Fatty Acid-Binding Proteins / metabolism
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Gene Expression Profiling
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Gene Expression Regulation*
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Mice
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Mice, Knockout
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Muscle, Skeletal / cytology
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Muscle, Skeletal / metabolism*
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Myoblasts / cytology
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Myoblasts / metabolism
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Myosins / metabolism
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism*
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Nuclear Receptor Interacting Protein 1
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Oligonucleotide Array Sequence Analysis
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Oxidation-Reduction
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Oxygen Consumption*
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PPAR delta / metabolism
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Protein Isoforms / metabolism
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Receptors, Estrogen / metabolism
Substances
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Adaptor Proteins, Signal Transducing
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Cadherins
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Fabp3 protein, mouse
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Fatty Acid Binding Protein 3
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Fatty Acid-Binding Proteins
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Nuclear Proteins
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Nuclear Receptor Interacting Protein 1
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PPAR delta
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Protein Isoforms
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Receptors, Estrogen
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M-cadherin
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Myosins