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Mol Cell Biochem. 2018 Jul;444(1-2):109-123. doi: 10.1007/s11010-017-3236-1. Epub 2017 Nov 30.

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

Author information

1
Stem Cells, Ageing and Molecular Physiology Research (SCAMP) Unit, Exercise Metabolism and Adaptation Research Group (EMARG), Research Institute for Sport and Exercise Sciences (RISES), Liverpool John Moores University, Liverpool, UK.
2
Department of Internal Medicine, Division of Endocrinology and Metabolism, Carver College of Medicine, University of Iowa, Iowa City, IA, 52246, USA.
3
Centre for Applied Sport and Exercise Sciences, University of Central Lancashire, Preston, UK.
4
Department of Sport and Health Sciences, College of Life and Environmental Sciences, University of Exeter, Exeter, UK.
5
School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK.
6
Institute for Science and Technology in Medicine (ISTM), School of Medicine, Keele University, The Guy Hilton Research Centre, Thornburrow Drive, Hartshill, Staffordshire, ST4 7QB, UK. a.p.sharples@googlemail.com.
7
Stem Cells, Ageing and Molecular Physiology Research (SCAMP) Unit, Exercise Metabolism and Adaptation Research Group (EMARG), Research Institute for Sport and Exercise Sciences (RISES), Liverpool John Moores University, Liverpool, UK. a.p.sharples@googlemail.com.

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.

KEYWORDS:

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

PMID:
29189984
PMCID:
PMC6002440
DOI:
10.1007/s11010-017-3236-1
[Indexed for MEDLINE]
Free PMC Article

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