title: Reduced skeletal muscle fiber size following caloric restriction is associated with calpain-mediated proteolysis and attenuation of IGF-1 signaling.
abstract: Caloric restriction decreases skeletal muscle mass in mammals, principally due to a reduction in fiber size. The effect of suboptimal nutrient intake on skeletal muscle metabolic properties in neonatal calves was examined. The longissimus muscle (LM) was collected after a control (CON) or caloric restricted (CR) diet was cosnumed for 8 wk and muscle fiber size, gene expression, and metabolic signal transduction activity were measured. Results revealed that CR animals had smaller (P< 0.05) LM fiber cross-sectional area than CON, as expected. Western blot analysis detected equivalent amounts of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) but reduced (P< 0.05) amounts of the splice-variant, PGC1α-4 in CR LM. Expression ofIGF-1, a PGC1α-4 target gene, was 40% less (P< 0.05) in CR than CON. Downstream mediators of autocrine IGF-1 signaling also are attenuated in CR by comparison with CON. The amount of phosphorylated AKT1 was less (P< 0.05) in CR than CON. The ratio of p4EBP1T37/46to total 4EBP1, a downstream mediator of AKT1, did not differ between CON and CR. By contrast, protein lysates from CR LM contained less (P< 0.05) total glycogen synthase kinase-3β (GSK3β) and phosphorylated GSK3β than CON LM, suggesting blunted protein synthesis. Smaller CR LM fiber size associates with increased (P< 0.05) calpain 1 (CAPN1) activity coupled with lower (P< 0.05) expression ofcalpastatin, the endogenous inhibitor of CAPN1.Atrogin-1andMuRFexpression and autophagy components were unaffected by CR. Thus CR suppresses the hypertrophic PGC1α-4/IGF-1/AKT1 pathway while promoting activation of the calpain system.
authors.affiliation: Department of Animal and Poultry Sciences, Virginia Polytechnic Institute and State University, Blacksburg Virginia; and.
authors.forename: Yue
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Animal and Poultry Sciences, Virginia Polytechnic Institute and State University, Blacksburg Virginia; and.
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Bradley
authors.affiliation: Department of Animal and Poultry Sciences, Virginia Polytechnic Institute and State University, Blacksburg Virginia; and.
authors.forename: Sarah R
authors.initials: SR
authors.lastname: McCoski
authors.affiliation: Department of Animal Sciences and Industry, Kansas State University, Manhattan, Kansas.
authors.forename: John M
authors.initials: JM
authors.lastname: Gonzalez
authors.affiliation: Department of Animal and Poultry Sciences, Virginia Polytechnic Institute and State University, Blacksburg Virginia; and.
authors.forename: Alan D
authors.initials: AD
authors.lastname: Ealy
authors.affiliation: Department of Animal and Poultry Sciences, Virginia Polytechnic Institute and State University, Blacksburg Virginia; and sealy@vt.edu.
authors.forename: Sally E
authors.identifier: 0000-0002-9514-4220
authors.initials: SE
authors.lastname: Johnson
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D031204:Caloric Restriction / Q000379:methods*; D002154:Calpain / Q000378:metabolism*; D002417:Cattle; D048429:Cell Size; D002478:Cells, Cultured; D002149:Energy Intake / Q000502:physiology*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D018485:Muscle Fibers, Skeletal / Q000166:cytology* / Q000502:physiology*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000378:metabolism; D059748:Proteolysis
chemical_list: D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D007334:Insulin-Like Growth Factor I; D002154:Calpain
keywords: IGF-1; PGC1α; caloric restriction; calpain; skeletal muscle