Cited by 35Muscle Physiology and DisordersMuscle metabolism and nutritionMeat and Animal Product Quality

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

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Lu, Yue, Bradley, Jennifer S., McCoski, Sarah R., Gonzalez, John M., Ealy, Alan D., Johnson, Sally E.·2017·American Journal of Physiology-Regulatory, Integrative and Comparative Physiology

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 of IGF-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 p4EBP1T37/46 to 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 of calpastatin, the endogenous inhibitor of CAPN1. Atrogin-1 and MuRF 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.

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Crossref · 10.1152/ajpregu.00400.2016

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Authors
Lu, Y., Bradley, J. S., McCoski, S. R., Gonzalez, J. M., Ealy, A. D., & Johnson, S. E.
Affiliations
  • Virginia Tech (US)
  • Kansas State University (US)
Corresponding author
Johnson, Sally E.
Venue
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
Published
2017-05-01
Volume
312
Issue
5
Pages
R806-R815
ISSN
  • 0363-6119 (ISSN-L)
  • 1522-1490
OpenAlex
W2591363413
Cited by
35
References
79
Citations by year
2026: 1 · 2025: 3 · 2024: 3 · 2023: 4 · 2022: 3 · 2021: 10 · 2020: 3 · 2019: 2 · 2018: 5 · 2016: 1
FWCI
1.12
Type
journal article
Language
en
Open access
Locations
  • American Journal of Physiology-Regulatory, Integrative and Comparative Physiology (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
USDA | National Institute of Food and Agriculture (NIFA) (2014-67015-21605)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
  • Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Meat and Animal Product Quality
Keywords
caloric restriction, calpain, calpastatin, IGF-1 signaling, AKT1, glycogen synthase kinase-3β, muscle atrophy, neonatal calves, longissimus dorsi, protein synthesis, autophagy
MeSH terms
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Animals, Animals, Newborn, Energy Intake, Calpain, Cattle, Cells, Cultured, Female, Insulin-Like Growth Factor I, Muscle Fibers, Skeletal, Gene Expression Regulation, Developmental, Caloric Restriction, Cell Size, Proteolysis

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