The omega-3 fatty acid, eicosapentaenoic acid (EPA), prevents the damaging effects of tumour necrosis factor (TNF)-alpha during murine skeletal muscle cell differentiation.
BACKGROUND
Eicosapentaenoic acid (EPA) is a omega-3 polyunsaturated fatty acid with anti-inflammatory and anti-cachetic properties that may have potential benefits with regards to skeletal muscle atrophy conditions where inflammation is present. It is also reported that pathologic levels of the pro-inflammatory cytokine tumour necrosis factor (TNF)-alpha are associated with muscle wasting, exerted through inhibition of myogenic differentiation and enhanced apoptosis. These findings led us to hypothesize that EPA may have a protective effect against skeletal muscle damage induced by the actions of TNF-alpha.


RESULTS
The deleterious effects of TNF-alpha on C2C12 myogenesis were completely inhibited by co-treatment with EPA. Thus, EPA prevented the TNF-mediated loss of MyHC expression and significantly increased myogenic fusion (p < 0.05) and myotube diameter (p < 0.05) indices back to control levels. EPA protective activity was associated with blocking cell death pathways as EPA completely attenuated TNF-mediated increases in caspase-8 activity (p < 0.05) and cellular necrosis (p < 0.05) back to their respective control levels. EPA alone significantly reduced spontaneous apoptosis and necrosis of differentiating myotubes (p < 0.001 and p < 0.05, respectively). A 2 hour pre-treatment with EPA, prior to treatment with TNF alone, gave similar results.


CONCLUSIONS
In conclusion, EPA has a protective action against the damaging effects of TNF-alpha on C2C12 myogenesis. These findings support further investigations of EPA as a potential therapeutic agent during skeletal muscle regeneration following injury.
Magee
Peter
P
Biomedical Sciences Research Institute, University of Salford, Manchester, M5 4WT, UK. p.magee@pgr.salford.ac.uk
Pearson
Stephen
S
Allen
Jeremy
J
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D004336:Drug Antagonism; D015118:Eicosapentaenoic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D032342:Muscle Cells / Q000166:cytology / Q000187:drug effects; D024510:Muscle Development / Q000187:drug effects; D018485:Muscle Fibers, Skeletal; D018482:Muscle, Skeletal / Q000166:cytology*; D009336:Necrosis / Q000188:drug therapy / Q000517:prevention & control; D020011:Protective Agents; D014409:Tumor Necrosis Factor-alpha / Q000009:adverse effects*
D015525:Fatty Acids, Omega-3; D020011:Protective Agents; D014409:Tumor Necrosis Factor-alpha; D015118:Eicosapentaenoic Acid