Cocoa flavanols have been shown to improve muscle function and may offer a novel approach to protect against muscle atrophy. Hippuric acid (HA) is a colonic metabolite of (-)-epicatechin (EPI), the primary bioactive compound of cocoa, and may be responsible for the associations between cocoa supplementation and muscle metabolic alterations. Accordingly, we investigated the effects of EPI and HA upon skeletal muscle morphology and metabolism within an in vitro model of muscle atrophy. Under atrophy-like conditions (24h 100μM dexamethasone (DEX)), C2C12 myotube diameter was significantly greater following co-incubation with either 25μM HA (11.19±0.39μm) or 25μM EPI (11.01±0.21μm) compared to the vehicle control (VC; 7.61±0.16μm, both P < .001). In basal and leucine-stimulated states, there was a significant reduction in myotube protein synthesis (MPS) rates following DEX treatment in VC (P = .024). Interestingly, co-incubation with EPI or HA abrogated the DEX-induced reductions in MPS rates, whereas no significant differences versus control treated myotubes (CTL) were noted. Furthermore, co-incubation with EPI or HA partially attenuated the increase in proteolysis seen in DEX-treated cells, preserving LC3 α/β II:I and caspase-3 protein expression in atrophy-like conditions. The protein content of PGC1α, ACC, and TFAM (regulators of mitochondrial function) were significantly lower in DEX-treated versus. CTL cells (all P < .050). However, co-incubation with EPI or HA was unable to prevent these DEX-induced alterations. For the first time we demonstrate that EPI and HA exert anti-atrophic effects on C2C12 myotubes, providing novel insight into the association between flavanol supplementation and favourable effects on muscle health.
KEYWORDSMuscle atrophy
dexamethasone
mitochondria
flavanols
epicatechin
hippuric acid
Abbreviations4EBP1eukaryotic initiation factor 4E binding protein 1
ACCacetyl-CoA carboxylase
AMPKα5′ AMP-activated protein kinase
CTL24h control (no atrophic stimulus)
DEX24h 100μM dexamethasone treatment
25μM epicatechin supplementationHA
24h25μM hippuric acid supplementation
LC3 α/βmicrotubule-associated proteins 1A/1B light chain 3B
LEU90mins of 5mM leucine stimulation
MAFbxmuscle atrophy f-box
mTORC1total mechanistic target of rapamycin
MURF-1muscle ring finger protein 1
PGC1αperoxisome proliferator-activated receptor gamma coactivator 1-alpha
S6K1ribosomal protein S6 kinase beta-1
TFAMmitochondrial transcription factor A
VCethanol matched vehicle control
© 2022 The Author(s). Published by Elsevier Inc.
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