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Glucocorticoids enhance muscle endurance and ameliorate Duchenne muscular dystrophy through a defined metabolic program

Morrison-Nozik, Alexander, Anand, Priti, Zhu, Han, Duan, Qiming, Sabeh, Mohamad, Prosdocimo, Domenick A., Lemieux, Madeleine E., Nordsborg, Nikolai, Russell, Aaron P., MacRae, Calum A., Gerber, Anthony N., Jain, Mukesh K. and Haldar, Saptarsi M. 2015, Glucocorticoids enhance muscle endurance and ameliorate Duchenne muscular dystrophy through a defined metabolic program, Proceedings of the national academy of sciences of the United States of America, vol. 112, no. 49, pp. E6780-E6789, doi: 10.1073/pnas.1512968112.

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Title Glucocorticoids enhance muscle endurance and ameliorate Duchenne muscular dystrophy through a defined metabolic program
Author(s) Morrison-Nozik, Alexander
Anand, Priti
Zhu, Han
Duan, Qiming
Sabeh, Mohamad
Prosdocimo, Domenick A.
Lemieux, Madeleine E.
Nordsborg, Nikolai
Russell, Aaron P.ORCID iD for Russell, Aaron P. orcid.org/0000-0002-7323-9501
MacRae, Calum A.
Gerber, Anthony N.
Jain, Mukesh K.
Haldar, Saptarsi M.
Journal name Proceedings of the national academy of sciences of the United States of America
Volume number 112
Issue number 49
Start page E6780
End page E6789
Total pages 10
Publisher National Academy of Sciences
Place of publication Washington, D.C.
Publication date 2015-12-08
ISSN 1091-6490
Keyword(s) Duchenne muscular dystrophy
exercise
glucocorticoid
skeletal muscle metabolism
steroid hormone nuclear receptor
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
DEFICIENT MDX MOUSE
SKELETAL-MUSCLE
GENE-EXPRESSION
EXERCISE PERFORMANCE
SUBMAXIMAL EXERCISE
PREDNISOLONE INTAKE
MAGNETIC-RESONANCE
ENERGY-METABOLISM
RECEPTOR ACTIVITY
LIPID-METABOLISM
Summary Classic physiology studies dating to the 1930s demonstrate that moderate or transient glucocorticoid (GC) exposure improves muscle performance. The ergogenic properties of GCs are further evidenced by their surreptitious use as doping agents by endurance athletes and poorly understood efficacy in Duchenne muscular dystrophy (DMD), a genetic muscle-wasting disease. A defined molecular basis underlying these performance-enhancing properties of GCs in skeletal muscle remains obscure. Here, we demonstrate that ergogenic effects of GCs are mediated by direct induction of the metabolic transcription factor KLF15, defining a downstream pathway distinct from that resulting in GC-related muscle atrophy. Furthermore, we establish that KLF15 deficiency exacerbates dystrophic severity and muscle GC-KLF15 signaling mediates salutary therapeutic effects in the mdx mouse model of DMD. Thus, although glucocorticoid receptor (GR)-mediated transactivation is often associated with muscle atrophy and other adverse effects of pharmacologic GC administration, our data define a distinct GR-induced gene regulatory pathway that contributes to therapeutic effects of GCs in DMD through proergogenic metabolic programming.
Language eng
DOI 10.1073/pnas.1512968112
Field of Research 110604 Sports Medicine
Socio Economic Objective 929999 Health not elsewhere classified
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2015, National Academy of Sciences
Persistent URL http://hdl.handle.net/10536/DRO/DU:30081269

Document type: Journal Article
Collection: School of Exercise and Nutrition Sciences
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