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Regulation of the nuclear hormone receptor nur77 in muscle: Influence of exercise-activated pathways in vitro and obesity in vivo


Regular physical exercise is well known to improve glucose and lipid metabolism in skeletal muscle. However, the transcription factors regulating these adaptive changes are not well-characterised. Recently the nuclear orphan receptor nur77 was shown to be induced by exercise and linked to regulation of metabolic gene expression in skeletal muscle. In this study we investigated the regulation of nur77 in muscle by different exercise-activated pathways. Nur77 expression was found to be responsive to adrenergic stimulation and calcium influx, but not to activation of the AMP dependent kinase. These results identify the adrenergic-cyclic AMP-PKA pathway to be the most potent activator of nur77 expression in muscle and therefore the likely cause of increased expression after exercise. We also identified nur77 expression to be reduced in the muscle of obese/insulin resistant rats after high fat feeding. Furthermore exposure to fatty acids, insulin or inflammation was not the cause of decreased nur77 expression in insulin resistant muscle. This suggests a reduced responsiveness to adrenergic stimulation as the likely cause of diminished nur77 expression in muscle of high fat fed rats, which has been observed in obese/insulin resistant individuals. Our results suggest adrenergic stimulation as the most important stimulus for nur77 expression and point to a significant role for this transcription factor in adaptive changes in muscle after exercise and in insulin resistant states.

Type Journal
ISBN 0006-3002 (Print)
Authors Kanzleiter, T.; Wilks, D.; Preston, E.; Ye, J.; Frangioudakis, G.; Cooney, G. J.;
Publisher Name BBA-MOL BASIS DIS
Published Date 2009-08-01
Published Volume 1792
Published Issue 8
Published Pages 777-82
Status Published in-print
URL link to publisher's version
OpenAccess link to author's accepted manuscript version