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Akt signalling through GSK‐3β, mTOR and Foxo1 is involved in human skeletal muscle hypertrophy and atrophy
Author(s) -
Léger Bertrand,
Cartoni Romain,
Praz Manu,
Lamon Séverine,
Dériaz Olivier,
Crettenand Antoinette,
Gobelet Charles,
Rohmer Paul,
Konzelmann Michel,
Luthi François,
Russell Aaron P.
Publication year - 2006
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2006.116715
Subject(s) - foxo1 , protein kinase b , muscle hypertrophy , pi3k/akt/mtor pathway , endocrinology , medicine , skeletal muscle , muscle atrophy , anabolism , atrophy , p70 s6 kinase 1 , biology , phosphorylation , signal transduction , microbiology and biotechnology
Skeletal muscle size is tightly regulated by the synergy between anabolic and catabolic signalling pathways which, in humans, have not been well characterized. Akt has been suggested to play a pivotal role in the regulation of skeletal muscle hypertrophy and atrophy in rodents and cells. Here we measured the amount of phospho‐Akt and several of its downstream anabolic targets (glycogen synthase kinase‐3β (GSK‐3β), mTOR, p70 s6k and 4E‐BP1) and catabolic targets (Foxo1, Foxo3, atrogin‐1 and MuRF1). All measurements were performed in human quadriceps muscle biopsies taken after 8 weeks of both hypertrophy‐stimulating resistance training and atrophy‐stimulating de‐training. Following resistance training a muscle hypertrophy (∼10%) and an increase in phospho‐Akt, phospho‐GSK‐3β and phospho‐mTOR protein content were observed. This was paralleled by a decrease in Foxo1 nuclear protein content. Following the de‐training period a muscle atrophy (5%), relative to the post‐training muscle size, a decrease in phospho‐Akt and GSK‐3β and an increase in Foxo1 were observed. Atrogin‐1 and MuRF1 increased after the hypertrophy and decreased after the atrophy phases. We demonstrate, for the first time in human skeletal muscle, that the regulation of Akt and its downstream signalling pathways GSK‐3β, mTOR and Foxo1 are associated with both the skeletal muscle hypertrophy and atrophy processes.