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: To further address the role of SGK1 in skeletal muscle maintenance, we evaluated skeletal muscle composition and function in mice lacking sgk1. These mice exhibit impaired renal sodium retention but the muscle phenotype has not been studied (Wulff et al, 2002). Mice deficient for sgk1 showed no changes in body mass but revealed decreased weight of the TA muscles (Supporting Information Fig S2F). Histological evaluation of skeletal muscles of sgk1−/− mice demonstrated increased variation of fiber size with numerous small and rounded myofibers (Fig 4A). Morphometric data confirmed that sgk1−/− mice had decreased muscle fiber size in the TA, gastrocnemius and soleus muscles (Fig 4B and Supporting Information Fig S3E). Fiber type analysis of gastrocnemius and TA muscles did not reveal changes in fiber type composition (Supporting Information Fig S2G). Despite the decrease in muscle fiber size, skeletal muscle of sgk1−/− mice showed an increase in phosphorylated Akt (Fig 4C and Supporting Information Fig S3A). Levels of phosphorylated Foxo3a at S315 were decreased in sgk1−/− mice, whereas levels of phospho-Foxo3a at S253, LC3B and p62 were unchanged (Supporting Information Fig S3B).
Affiliation: McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.