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Activation of serum/glucocorticoid-induced kinase 1 (SGK1) is important to maintain skeletal muscle homeostasis and prevent atrophy.

Andres-Mateos E, Brinkmeier H, Burks TN, Mejias R, Files DC, Steinberger M, Soleimani A, Marx R, Simmers JL, Lin B, Finanger Hedderick E, Marr TG, Lin BM, Hourdé C, Leinwand LA, Kuhl D, Föller M, Vogelsang S, Hernandez-Diaz I, Vaughan DK, Alvarez de la Rosa D, Lang F, Cohn RD - EMBO Mol Med (2012)

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.

View Article: PubMed Central - PubMed

Affiliation: McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

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Related in: MedlinePlus

Normal skeletal muscle morphology in hibernating squirrelsLeft column, an active summer squirrel; right column, a torpid squirrel.The morphology of quadriceps is unchanged by hibernation as seen in haematoxylin and eosin (H&E) stained sections (scale bar 90 µm).Dystrophin staining was performed to outline the sarcolemma to determine percentage distribution of minimum Feret's diameter.Average ± SD of minimum Feret's diameter in quadriceps (p = 0.26) and tibialis anterior (p = 0.33) muscles is not significantly different between summer and hibernation.
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fig01: Normal skeletal muscle morphology in hibernating squirrelsLeft column, an active summer squirrel; right column, a torpid squirrel.The morphology of quadriceps is unchanged by hibernation as seen in haematoxylin and eosin (H&E) stained sections (scale bar 90 µm).Dystrophin staining was performed to outline the sarcolemma to determine percentage distribution of minimum Feret's diameter.Average ± SD of minimum Feret's diameter in quadriceps (p = 0.26) and tibialis anterior (p = 0.33) muscles is not significantly different between summer and hibernation.

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.


Activation of serum/glucocorticoid-induced kinase 1 (SGK1) is important to maintain skeletal muscle homeostasis and prevent atrophy.

Andres-Mateos E, Brinkmeier H, Burks TN, Mejias R, Files DC, Steinberger M, Soleimani A, Marx R, Simmers JL, Lin B, Finanger Hedderick E, Marr TG, Lin BM, Hourdé C, Leinwand LA, Kuhl D, Föller M, Vogelsang S, Hernandez-Diaz I, Vaughan DK, Alvarez de la Rosa D, Lang F, Cohn RD - EMBO Mol Med (2012)

Normal skeletal muscle morphology in hibernating squirrelsLeft column, an active summer squirrel; right column, a torpid squirrel.The morphology of quadriceps is unchanged by hibernation as seen in haematoxylin and eosin (H&E) stained sections (scale bar 90 µm).Dystrophin staining was performed to outline the sarcolemma to determine percentage distribution of minimum Feret's diameter.Average ± SD of minimum Feret's diameter in quadriceps (p = 0.26) and tibialis anterior (p = 0.33) muscles is not significantly different between summer and hibernation.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3569655&req=5

fig01: Normal skeletal muscle morphology in hibernating squirrelsLeft column, an active summer squirrel; right column, a torpid squirrel.The morphology of quadriceps is unchanged by hibernation as seen in haematoxylin and eosin (H&E) stained sections (scale bar 90 µm).Dystrophin staining was performed to outline the sarcolemma to determine percentage distribution of minimum Feret's diameter.Average ± SD of minimum Feret's diameter in quadriceps (p = 0.26) and tibialis anterior (p = 0.33) muscles is not significantly different between summer and hibernation.
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.

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.

View Article: PubMed Central - PubMed

Affiliation: McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Show MeSH
Related in: MedlinePlus