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Reduced carbohydrate availability enhances exercise-induced p53 signalling in human skeletal muscle: implications for mitochondrial biogenesis.
MedLine Citation:
PMID:  23364526     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The mechanisms that regulate the enhanced skeletal muscle oxidative capacity observed when training with reduced carbohydrate (CHO) availability are currently unknown. The aim of the present study was to test the hypothesis that reduced CHO availability enhances p53 signalling and expression of genes associated with regulation of mitochondrial biogenesis and substrate utilisation in human skeletal muscle. In a repeated measures design, muscle biopsies (vastus lateralis) were obtained from eight active males before and after performing an acute bout of high-intensity interval running with either high (HIGH) or low CHO availability (LOW). Resting muscle glycogen (HIGH, 467 ± 19; LOW, 103 ± 9 mmol.kg(-1) dw) was greater in HIGH compared with LOW (P<0.05). Phosphorylation (P-) of ACC(Ser79) (HIGH, 1.4 ± 0.4; LOW, 2.9 ± 0.9) and p53(Ser15) (HIGH, 0.9 ± 0.4; LOW, 2.6 ± 0.8) was higher in LOW immediately post- and 3 h post-exercise, respectively (P<0.05). Before and 3 h post-exercise, mRNA content of PDK4, Tfam, COXIV and PGC-1α were greater in LOW compared with HIGH (P<0.05) whereas CPT1 showed trend towards significance (P=0.09). However, only PGC-1α expression was increased by exercise (P<0.05) where 3-fold increases occurred independent of CHO availability. We conclude that the exercise-induced increase in p53 phosphorylation is enhanced in conditions of reduced CHO availability which may be related to upstream signalling through AMPK. Given the emergence of p53 as a molecular regulator of mitochondrial biogenesis, such nutritional modulation of contraction-induced p53 activation has implications for both athletic and clinical populations.
Authors:
Jonathan D Bartlett; Jari Louhelainen; Zafar Iqbal; Andrew J R Cochran; Martin J Gibala; Warren Gregson; Graeme L Close; Barry Drust; James P Morton
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-30
Journal Detail:
Title:  American journal of physiology. Regulatory, integrative and comparative physiology     Volume:  -     ISSN:  1522-1490     ISO Abbreviation:  Am. J. Physiol. Regul. Integr. Comp. Physiol.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-31     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901230     Medline TA:  Am J Physiol Regul Integr Comp Physiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
1Liverpool John Moores University.
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