The transcriptional corepressor RIP140 regulates oxidative metabolism in skeletal muscle.
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.
Seth
Asha
A
Institute of Reproductive and Developmental Biology, Imperial College London, Du Cane Rd, London W12 ONN, UK.
Steel
Jennifer H
JH
Nichol
Donna
D
Pocock
Victoria
V
Kumaran
Mande K
MK
Fritah
Asmaa
A
Mobberley
Margaret
M
Ryder
Timothy A
TA
Rowlerson
Anthea
A
Scott
James
J
Poutanen
Matti
M
White
Roger
R
Parker
Malcolm
M
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D004734:Energy Metabolism; D000074026:Fatty Acid Binding Protein 3; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism*; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism; D009218:Myosins / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D000078723:Nuclear Receptor Interacting Protein 1; D020411:Oligonucleotide Array Sequence Analysis; D010084:Oxidation-Reduction; D010101:Oxygen Consumption; D047494:PPAR delta / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D000097983:ERRalpha Estrogen-Related Receptor
D048868:Adaptor Proteins, Signal Transducing; D015820:Cadherins; D000074026:Fatty Acid Binding Protein 3; D050556:Fatty Acid-Binding Proteins; D009218:Myosins; D009687:Nuclear Proteins; D000078723:Nuclear Receptor Interacting Protein 1; D047494:PPAR delta; D020033:Protein Isoforms; D011960:Receptors, Estrogen; D000097983:ERRalpha Estrogen-Related Receptor; C493409:Fabp3 protein, mouse; C070896:M-cadherin