title: Short-term feed deprivation rapidly induces the protein degradation pathway in skeletal muscles of young mice.
abstract: Analysis of protein kinase B (AKT) and S6 kinase1 (p70S6K) activity is widely used to assess the efficacy of interventions designed to increase or maintain skeletal muscle mass; these studies are often performed on feed-deprived mice. One problem associated with feed deprivation is that it promotes catabolism, and young or metabolically compromised mice may have less tolerance. The aim of our study was to determine the effect of various times of feed deprivation on the activity of AKT and p70S6K signaling and markers of protein catabolism in young, growing mice compared with adult mice. Young 23-d-old and adult 3-mo-old mice were feed deprived for 8, 10, and 12 h starting at 0700 h. In addition, adult mice were feed deprived for 24 h. AKT(Ser473) phosphorylation decreased by 50 and 76% from fed amounts by 10 and 12 h of feed deprivation, respectively, in young but not adult muscles. In adult muscles, feed deprivation for 24 h reduced AKT(Ser473) phosphorylation by 70%. Significant de-phosphorylation of p70S6K(Thr389) occurred in all feed-deprived young and adult mice. There was an increase in muscle RING-finger protein-1 (Murf1; 133-1245%) and muscle atrophy F-box protein or Atrogin-1 (Fbxo32; 210-2420%) mRNA in all young but not adult groups deprived of feed for 8-12 h, and there was a trend (P = 0.08) toward increased MURF1 associated with the contractile protein-enriched fraction isolated from young muscles of mice feed deprived for 12 h. This study demonstrates that skeletal muscles of young mice respond rapidly to feed deprivation by decreasing AKT activity and upregulating the protein degradation program.
authors: School of Anatomy, Physiology and Human Biology, University of Western Australia, Crawley, Western Australia, Australia. tea.shavlakadze@uwa.edu.au
authors: Tea
authors: T
authors: Shavlakadze
authors: Zoe
authors: Z
authors: Soffe
authors: Tahmina
authors: T
authors: Anwari
authors: Greg
authors: G
authors: Cozens
authors: Miranda D
authors: MD
authors: Grounds
mesh_terms: D000375:Aging; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D004435:Eating; D005508:Food Deprivation / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D059748:Proteolysis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D038601:Ribosomal Protein S6 / Q000378:metabolism; D044843:SKP Cullin F-Box Protein Ligases / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology; D013997:Time Factors; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D015854:Up-Regulation
chemical_list: D001786:Blood Glucose; D009124:Muscle Proteins; D012333:RNA, Messenger; D038601:Ribosomal Protein S6; D000070584:Tripartite Motif Proteins; C486691:Fbxo32 protein, mouse; D044843:SKP Cullin F-Box Protein Ligases; C499084:Trim63 protein, mouse; D044767:Ubiquitin-Protein Ligases; D051057:Proto-Oncogene Proteins c-akt; D046988:Proteasome Endopeptidase Complex