Maintaining skeletal muscle mass: lessons learned from hibernation.
Muscle disuse and starvation are often associated with a catabolic response leading to a dramatic loss of skeletal muscle mass. Hibernating animals represent a unique situation where muscle mass is maintained despite prolonged periods of immobilization and lack of nutrition. We analysed the molecular pathways upregulated during hibernation in an obligate hibernator, the 13-lined ground squirrel (Ictidomys tridecemlineatus). Although Akt has an established role in skeletal muscle maintenance, we found that activated Akt was decreased in skeletal muscle of hibernating squirrels. Another serine-threonine kinase, serum- and glucocorticoid-regulated kinase 1 (SGK1), was upregulated during hibernation and contributed to protection from loss of muscle mass via downregulation of proteolysis and autophagy and via an increase in protein synthesis. We extended our observations to non-hibernating animals and demonstrated that SGK1-null mice developed muscle atrophy. These mice displayed an exaggerated response to immobilization and starvation. Furthermore, SGK1 overexpression prevented immobilization-induced muscle atrophy. Taken together, our results identify SGK1 as a novel therapeutic target to combat skeletal muscle loss in acquired and inherited forms of muscle atrophy.
* The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada M5G 1X8. ronald.cohn@sickkids.ca.
Evgueni A
EA
Ivakine
Ronald D
RD
Cohn
D000818:Animals; D004195:Disease Models, Animal; D004734:Energy Metabolism; D005838:Genotype; D006605:Hibernation; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000201:enzymology* / Q000473:pathology; D009133:Muscular Atrophy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000517:prevention & control; D009929:Organ Size; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D012589:Sciuridae; D015398:Signal Transduction; D000099184:Serum-Glucocorticoid Regulated Kinases
D017874:Immediate-Early Proteins; D017346:Protein Serine-Threonine Kinases; D000099184:Serum-Glucocorticoid Regulated Kinases