Abstract
The role of the transcription factors sterol regulatory element binding protein 1a (SREBP-1a) and SREBP-1c in the regulation of cholesterol and fatty acid metabolism has been well studied; however, little is known about their specific function in muscle. In the present study, analysis of recent microarray data from muscle cells overexpressing SREBP1 suggested that they may play a role in the regulation of myogenesis. We then demonstrated that SREBP-1a and -1c inhibit myoblast-to-myotube differentiation and also induce in vivo and in vitro muscle atrophy. Furthermore, we have identified the transcriptional repressors BHLHB2 and BHLHB3 as mediators of these effects of SREBP-1a and -1c in muscle. Both repressors are SREBP-1 target genes, and they affect the expression of numerous genes involved in the myogenic program. Our findings identify a new role for SREBP-1 transcription factors in muscle, thus linking the control of muscle mass to metabolic pathways.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Basic Helix-Loop-Helix Transcription Factors / genetics
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Basic Helix-Loop-Helix Transcription Factors / metabolism
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Cell Differentiation
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Cells, Cultured
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Down-Regulation
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Homeodomain Proteins / genetics
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Homeodomain Proteins / metabolism
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Humans
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Male
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Mice
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Mice, Inbred BALB C
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Mice, Transgenic
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Muscle Development / genetics
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Muscle Development / physiology
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Muscle Fibers, Skeletal / cytology*
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Muscle Fibers, Skeletal / metabolism*
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Muscle, Skeletal / growth & development*
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Muscle, Skeletal / metabolism*
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Muscular Atrophy / etiology
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Myoblasts, Skeletal / cytology
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Myoblasts, Skeletal / metabolism
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Oligonucleotide Array Sequence Analysis
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Promoter Regions, Genetic
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Repressor Proteins / genetics
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Repressor Proteins / metabolism
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Sterol Regulatory Element Binding Protein 1 / genetics
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Sterol Regulatory Element Binding Protein 1 / metabolism*
Substances
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BHLHE40 protein, human
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BHLHE41 protein, human
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Basic Helix-Loop-Helix Transcription Factors
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Homeodomain Proteins
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Recombinant Proteins
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Repressor Proteins
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SREBF1 protein, human
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Sterol Regulatory Element Binding Protein 1