title: Activation of serum/glucocorticoid-induced kinase 1 (SGK1) is important to maintain skeletal muscle homeostasis and prevent atrophy.
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.
authors.affiliation: McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Eva
authors.initials: E
authors.lastname: Andres-Mateos
authors.forename: Heinrich
authors.initials: H
authors.lastname: Brinkmeier
authors.forename: Tyesha N
authors.initials: TN
authors.lastname: Burks
authors.forename: Rebeca
authors.initials: R
authors.lastname: Mejias
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Files
authors.forename: Martin
authors.initials: M
authors.lastname: Steinberger
authors.forename: Arshia
authors.initials: A
authors.lastname: Soleimani
authors.forename: Ruth
authors.initials: R
authors.lastname: Marx
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Simmers
authors.forename: Benjamin
authors.initials: B
authors.lastname: Lin
authors.forename: Erika
authors.initials: E
authors.lastname: Finanger Hedderick
authors.forename: Tom G
authors.initials: TG
authors.lastname: Marr
authors.forename: Brian M
authors.initials: BM
authors.lastname: Lin
authors.forename: Christophe
authors.initials: C
authors.lastname: Hourdé
authors.forename: Leslie A
authors.initials: LA
authors.lastname: Leinwand
authors.forename: Dietmar
authors.initials: D
authors.lastname: Kuhl
authors.forename: Michael
authors.initials: M
authors.lastname: Föller
authors.forename: Silke
authors.initials: S
authors.lastname: Vogelsang
authors.forename: Ivan
authors.initials: I
authors.lastname: Hernandez-Diaz
authors.forename: Dana K
authors.initials: DK
authors.lastname: Vaughan
authors.forename: Diego
authors.initials: D
authors.lastname: Alvarez de la Rosa
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
authors.forename: Ronald D
authors.initials: RD
authors.lastname: Cohn
mesh_terms: D000818:Animals; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D004789:Enzyme Activation; D005260:Female; D051858:Forkhead Transcription Factors / Q000037:antagonists & inhibitors; D006605:Hibernation / Q000502:physiology; D006706:Homeostasis; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D009133:Muscular Atrophy / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012589:Sciuridae; D015398:Signal Transduction; D013217:Starvation / Q000201:enzymology / Q000473:pathology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D017931:DNA Primers; D051858:Forkhead Transcription Factors; D017874:Immediate-Early Proteins; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D000099184:Serum-Glucocorticoid Regulated Kinases