title: Akt signalling through GSK-3beta, mTOR and Foxo1 is involved in human skeletal muscle hypertrophy and atrophy.
abstract: 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.
authors.affiliation: School of Exercise and Nutrition Sciences, Deakin University, 221 Burwood Highway 3125, Australia.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Léger
authors.forename: Romain
authors.initials: R
authors.lastname: Cartoni
authors.forename: Manu
authors.initials: M
authors.lastname: Praz
authors.forename: Séverine
authors.initials: S
authors.lastname: Lamon
authors.forename: Olivier
authors.initials: O
authors.lastname: Dériaz
authors.forename: Antoinette
authors.initials: A
authors.lastname: Crettenand
authors.forename: Charles
authors.initials: C
authors.lastname: Gobelet
authors.forename: Paul
authors.initials: P
authors.lastname: Rohmer
authors.forename: Michel
authors.initials: M
authors.lastname: Konzelmann
authors.forename: François
authors.initials: F
authors.lastname: Luthi
authors.forename: Aaron P
authors.initials: AP
authors.lastname: Russell
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000328:Adult; D001284:Atrophy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018797:Cell Cycle Proteins; D000071161:Forkhead Box Protein O1; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D006984:Hypertrophy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000235:genetics / Q000378:metabolism; D044843:SKP Cullin F-Box Protein Ligases / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D058570:TOR Serine-Threonine Kinases; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; C087000:EIF4EBP1 protein, human; C085126:FOXO1 protein, human; C499517:FOXO3 protein, human; D000071161:Forkhead Box Protein O1; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D009124:Muscle Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D000070584:Tripartite Motif Proteins; C440907:FBXO32 protein, human; D044843:SKP Cullin F-Box Protein Ligases; C440908:TRIM63 protein, human; D044767:Ubiquitin-Protein Ligases; D011494:Protein Kinases; C546842:MTOR protein, human; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; D038362:Glycogen Synthase Kinase 3