Maintaining skeletal muscle mass: lessons learned from hibernation
Evgueni A. Ivakine Experimental Physiology Accepted Article (Accepted 2014)
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 paradigm where muscle mass is maintained despite prolonged periods of immobilization and lack of nutrition. We analyzed molecular pathways upregulated during hibernation in an obligate hibernator 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 of loss of muscle mass via downregulation of proteolysis and autophagy and via increase in protein synthesis. We extended our observations to non-hibernating animals and demonstrated that
SGK1-null mice develop 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.
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