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Reduced skeletal muscle fiber size following caloric restriction is associated with calpain-mediated proteolysis and attenuation of IGF-1 signaling
Journal article   Open access   Peer reviewed

Reduced skeletal muscle fiber size following caloric restriction is associated with calpain-mediated proteolysis and attenuation of IGF-1 signaling

Yue Lu, Jennifer S Bradley, Sarah R McCoski, John M Gonzalez, Alan D Ealy and Sally E Johnson
American journal of physiology. Regulatory, integrative and comparative physiology, Vol.312(5), pp.R806-R815
05/01/2017
DOI: 10.1152/ajpregu.00400.2016
PMCID: PMC5451576
PMID: 28228415
url
https://doi.org/10.1152/ajpregu.00400.2016View
Published (Version of record) Open Access

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 ( < 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 ( < 0.05) amounts of the splice-variant, PGC1α-4 in CR LM. Expression of , a PGC1α-4 target gene, was 40% less ( < 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 ( < 0.05) in CR than CON. The ratio of p4EBP1 to total 4EBP1, a downstream mediator of AKT1, did not differ between CON and CR. By contrast, protein lysates from CR LM contained less ( < 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 ( < 0.05) calpain 1 (CAPN1) activity coupled with lower ( < 0.05) expression of , the endogenous inhibitor of CAPN1. and expression 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.
 Animals Animals, Newborn Caloric Restriction - methods Calpain - metabolism Cattle Cell Size Cells, Cultured Energy Intake - physiology Female Gene Expression Regulation, Developmental - physiology Insulin-Like Growth Factor I - metabolism Muscle Fibers, Skeletal - cytology Muscle Fibers, Skeletal - physiology Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha - metabolism Proteolysis

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