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The role of resveratrol on skeletal muscle cell differentiation and myotube hypertrophy during glucose restriction
Journal article   Open access   Peer reviewed

The role of resveratrol on skeletal muscle cell differentiation and myotube hypertrophy during glucose restriction

Hannah F. Dugdale, David C. Hughes, Robert Allan, Colleen S. Deane, Christopher R. Coxon, James P. Morton, Claire E. Stewart and Adam P. Sharples
Molecular and cellular biochemistry, Vol.444(1-2), pp.109-123
07/01/2018
DOI: 10.1007/s11010-017-3236-1
PMCID: PMC6002440
PMID: 29189984
url
https://doi.org/10.1007/s11010-017-3236-1View
Published (Version of record) Open Access

Abstract

Glucose restriction (GR) impairs muscle cell differentiation and evokes myotube atrophy. Resveratrol treatment in skeletal muscle cells improves inflammatory-induced reductions in skeletal muscle cell differentiation. We therefore hypothesised that resveratrol treatment would improve muscle cell differentiation and myotube hypertrophy in differentiating C2C12 myoblasts and mature myotubes during GR. Glucose restriction at 0.6 g/L (3.3 mM) blocked differentiation and myotube hypertrophy versus high-glucose (4.5 g/L or 25 mM) differentiation media (DM) conditions universally used for myoblast culture. Resveratrol (10 A mu M) treatment increased SIRT1 phosphorylation in DM conditions, yet did not improve differentiation when administered to differentiating myoblasts in GR conditions. Resveratrol did evoke increases in hypertrophy of mature myotubes under DM conditions with corresponding elevated Igf-I and Myhc7 gene expression, coding for the 'slow' type I MYHC protein isoform. Inhibition of SIRT1 via EX-527 administration (100 nM) also reduced myotube diameter and area in DM conditions and resulted in lower gene expression of Myhc 1, 2 and 4 coding for 'intermediate' and 'faster' IIx, IIa and IIb protein isoforms, respectively. Resveratrol treatment did not appear to modulate phosphorylation of energy-sensing protein AMPK or protein translation initiator P70S6K. Importantly, in mature myotubes, resveratrol treatment was able to ameliorate reduced myotube growth in GR conditions over an acute 24-h period, but not over 48-72 h. Overall, resveratrol evoked myotube hypertrophy in DM conditions while favouring 'slower' Myhc gene expression and acutely ameliorated impaired myotube growth observed during glucose restriction.
Cell Biology Life Sciences & Biomedicine Science & Technology

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