Activation of serum/glucocorticoid-induced kinase 1 (SGK1) is important to maintain skeletal muscle homeostasis and prevent atrophy.
Bottom Line: 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.Our results identify a novel therapeutic target to combat loss of skeletal muscle mass associated with muscle degeneration and atrophy.
Affiliation: McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.Show MeSH
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Mentions: Prolonged periods of immobilization and/or starvation cause significant muscle atrophy, defined by reduced muscle mass, muscle fiber size and muscle function, in various mammals including humans. Specifically, artificial limb immobilization in a mouse for 12–18 days causes a 45% loss of skeletal muscle mass, while mice deprived of food for 48 h lose approximately 15% muscle mass (Hudson & Franklin, 2002; Jagoe et al, 2002). Histological evaluation of quadriceps muscles collected from ground squirrels exposed to 6 months of immobility with no food or water intake and from active summer squirrels showed no morphological differences (Fig 1A and B). Muscles collected from the diaphragm, gastrocnemius and tibialis anterior (TA) also did not display variation in muscle architecture, composition or size between hibernating and summer squirrels. Supporting these observations, quantitative morphometric analysis of muscle fiber size revealed no significant changes in fiber size of quadriceps (composed of slow and fast muscle fibers) and TA muscles (mainly composed of fast muscle fibers) demonstrating preservation of muscle fiber size independently of fiber type composition (Fig 1C and D and Supporting Information Fig S1A). Despite extended periods of immobilization and starvation, which normally favour the development of muscle atrophy, the skeletal muscle mass, structure and morphometric values of the hibernating ground squirrel remain unchanged.
Affiliation: McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.