Activation of serum/glucocorticoid-induced kinase 1 (SGK1) is important to maintain skeletal muscle homeostasis and prevent atrophy

Eva Andres-Mateos, Heinrich Brinkmeier, Tyesha N. Burks, Rebeca Mejias, Daniel C. Files, Martin Steinberger, Arshia Soleimani, Ruth Marx, Jessica L. Simmers, Benjamin Lin, Erika Finanger Hedderick, Tom G. Marr, Brian M. Lin, Christophe Hourdé, Leslie A. Leinwand, Dietmar Kuhl, Michael Föller, Silke Vogelsang, Ivan Hernandez-Diaz, Dana K. VaughanDiego Alvarez de la Rosa, Florian Lang, Ronald D. Cohn

Research output: Contribution to journalArticle

61 Scopus citations

Abstract

Maintaining skeletal muscle mass is essential for general health and prevention of disease progression in various neuromuscular conditions. Currently, no treatments are available to prevent progressive loss of muscle mass in any of these conditions. Hibernating mammals are protected from muscle atrophy despite prolonged periods of immobilization and starvation. Here, we describe a mechanism underlying muscle preservation and translate it to non-hibernating mammals. Although Akt has an established role in skeletal muscle homeostasis, we find that serum- and glucocorticoid-inducible kinase 1 (SGK1) regulates muscle mass maintenance via downregulation of proteolysis and autophagy as well as increased protein synthesis during hibernation. We demonstrate that SGK1 is critical for the maintenance of skeletal muscle homeostasis and function in non-hibernating mammals in normal and atrophic conditions such as starvation and immobilization. Our results identify a novel therapeutic target to combat loss of skeletal muscle mass associated with muscle degeneration and atrophy.

Original languageEnglish (US)
Pages (from-to)80-91
Number of pages12
JournalEMBO Molecular Medicine
Volume5
Issue number1
DOIs
StatePublished - Jan 1 2013

Keywords

  • Hibernation
  • Muscle atrophy
  • Muscle homeostasis
  • Muscle hypertrophy
  • SGK1

ASJC Scopus subject areas

  • Molecular Medicine

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    Andres-Mateos, E., Brinkmeier, H., Burks, T. N., Mejias, R., Files, D. C., Steinberger, M., Soleimani, A., Marx, R., Simmers, J. L., Lin, B., Finanger Hedderick, E., Marr, T. G., Lin, B. M., Hourdé, C., Leinwand, L. A., Kuhl, D., Föller, M., Vogelsang, S., Hernandez-Diaz, I., ... Cohn, R. D. (2013). Activation of serum/glucocorticoid-induced kinase 1 (SGK1) is important to maintain skeletal muscle homeostasis and prevent atrophy. EMBO Molecular Medicine, 5(1), 80-91. https://doi.org/10.1002/emmm.201201443