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Nur77 Coordinately Regulates Expression of Genes Linked to Glucose Metabolism in Skeletal Muscle
- Source :
- Molecular Endocrinology. 21:2152-2163
- Publication Year :
- 2007
- Publisher :
- The Endocrine Society, 2007.
-
Abstract
- Innervation is important for normal metabolism in skeletal muscle, including insulin-sensitive glucose uptake. However, the transcription factors that transduce signals from the neuromuscular junction to the nucleus and affect changes in metabolic gene expression are not well defined. We demonstrate here that the orphan nuclear receptor Nur77 is a regulator of gene expression linked to glucose utilization in muscle. In vivo, Nur77 is preferentially expressed in glycolytic compared with oxidative muscle and is responsive to β-adrenergic stimulation. Denervation of rat muscle compromises expression of Nur77 in parallel with that of numerous genes linked to glucose metabolism, including glucose transporter 4 and genes involved in glycolysis, glycogenolysis, and the glycerophosphate shuttle. Ectopic expression of Nur77, either in rat muscle or in C2C12 muscle cells, induces expression of a highly overlapping set of genes, including glucose transporter 4, muscle phosphofructokinase, and glycogen phosphorylase. Furthermore, selective knockdown of Nur77 in rat muscle by small hairpin RNA or genetic deletion of Nur77 in mice reduces the expression of a battery of genes involved in skeletal muscle glucose utilization in vivo. Finally, we show that Nur77 binds the promoter regions of multiple genes involved in glucose metabolism in muscle. These results identify Nur77 as a potential mediator of neuromuscular signaling in the control of metabolic gene expression.
- Subjects :
- Receptors, Steroid
Glucose uptake
Neuromuscular Junction
Receptors, Cytoplasmic and Nuclear
Biology
Article
Cell Line
Mice
Endocrinology
Gene expression
Nuclear Receptor Subfamily 4, Group A, Member 1
medicine
Animals
Myocyte
Muscle, Skeletal
Molecular Biology
Regulation of gene expression
Gene knockdown
Glucose transporter
Skeletal muscle
General Medicine
Rats
DNA-Binding Proteins
Glucose
medicine.anatomical_structure
Gene Expression Regulation
Biochemistry
Ectopic expression
Signal Transduction
Transcription Factors
Subjects
Details
- ISSN :
- 19449917 and 08888809
- Volume :
- 21
- Database :
- OpenAIRE
- Journal :
- Molecular Endocrinology
- Accession number :
- edsair.doi.dedup.....6ac650534db7312935c5932fb8f75956