Akt signalling through GSK-3beta, mTOR and Foxo1 is involved in human skeletal muscle hypertrophy and atrophy.

Journal Article (Journal Article)

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-3beta (GSK-3beta), 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 ( approximately 10%) and an increase in phospho-Akt, phospho-GSK-3beta 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-3beta 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-3beta, mTOR and Foxo1 are associated with both the skeletal muscle hypertrophy and atrophy processes.

Full Text

Duke Authors

Cited Authors

  • Léger, B; Cartoni, R; Praz, M; Lamon, S; Dériaz, O; Crettenand, A; Gobelet, C; Rohmer, P; Konzelmann, M; Luthi, F; Russell, AP

Published Date

  • November 1, 2006

Published In

Volume / Issue

  • 576 / Pt 3

Start / End Page

  • 923 - 933

PubMed ID

  • 16916907

Pubmed Central ID

  • PMC1890416

International Standard Serial Number (ISSN)

  • 0022-3751

Digital Object Identifier (DOI)

  • 10.1113/jphysiol.2006.116715


  • eng

Conference Location

  • England