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, Adam P. Sharples

Research output: Contribution to journalArticle

11 Citations (Scopus)
1 Downloads (Pure)

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 µM) 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.

Original languageEnglish
Pages (from-to)109-123
Number of pages15
JournalMolecular and Cellular Biochemistry
Volume444
Issue number1-2
Early online date30 Nov 2017
DOIs
Publication statusPublished - Jul 2018

Keywords

  • AMPK
  • Atrophy
  • Dietary restriction
  • Hypertrophy
  • MYHC
  • Myoblasts
  • P70S6K
  • SIRT1

ASJC Scopus subject areas

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

Fingerprint Dive into the research topics of 'The role of resveratrol on skeletal muscle cell differentiation and myotube hypertrophy during glucose restriction'. Together they form a unique fingerprint.

Cite this