Reduced skeletal muscle fiber size following caloric restriction is associated with calpain-mediated proteolysis and attenuation of IGF-1 signaling
Open accessAbstract
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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During CR without RT, blunted muscle protein synthesis with elevated proteolysis might allow energy maintenance.
“During CR without RT, the blunted muscle protein synthesis with elevated proteolysis might allow energy maintenance [32].”
From Resistance Training Prevents Muscle Loss Induced by Caloric Restriction in Obese Elderly Individuals: A Systematic Review and Meta-Analysis (2018) · cites this paper as [32]
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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
- Publisher
- American Physiological Society
- Published
- 2017-05-01
- Volume
- 312
- Issue
- 5
- Pages
- R806-R815
- ISSN
- 0363-6119 (ISSN-L)
- 1522-1490
- PMC
- PMC5451576
- 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
- green
- www.ncbi.nlm.nih.gov
- 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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