Journal
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
Volume 312, Issue 5, Pages R806-R815Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpregu.00400.2016
Keywords
skeletal muscle; calpain; IGF-1; PGC1 alpha; caloric restriction
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Funding
- National Institute of Food and Agriculture, US Department of Agriculture [2014-67015-21605]
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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-gamma coactivator-1 alpha (PGC1 alpha) but reduced (P < 0.05) amounts of the splice-variant, PGC1 alpha-4 in CR LM. Expression of IGF-1, a PGC1 alpha-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-3 beta (GSK3 beta) and phosphorylated GSK3 beta 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 PGC1 alpha-4/IGF-1/AKT1 pathway while promoting activation of the calpain system.
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