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EMBO Mol Med ; 5(1): 80-91, 2013 01.
Article in English | MEDLINE | ID: mdl-23161797

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.


Subject(s)
Immediate-Early Proteins/metabolism , Muscle, Skeletal/enzymology , Muscular Atrophy/prevention & control , Protein Serine-Threonine Kinases/metabolism , Animals , Base Sequence , DNA Primers/genetics , Enzyme Activation , Female , Forkhead Transcription Factors/antagonists & inhibitors , Hibernation/physiology , Homeostasis , Immediate-Early Proteins/genetics , Male , Mice , Mice, Transgenic , Muscle, Skeletal/pathology , Muscle, Skeletal/physiopathology , Muscular Atrophy/pathology , Muscular Atrophy/physiopathology , Protein Serine-Threonine Kinases/genetics , Proto-Oncogene Proteins c-akt/metabolism , Sciuridae , Signal Transduction , Starvation/enzymology , Starvation/pathology , TOR Serine-Threonine Kinases/metabolism
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