Abstract
BackgroundEicosapentaenoic acid (EPA) is a ώ-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)-α 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-α.ResultsThe deleterious effects of TNF-α 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.ConclusionIn conclusion, EPA has a protective action against the damaging effects of TNF-α on C2C12 myogenesis. These findings support further investigations of EPA as a potential therapeutic agent during skeletal muscle regeneration following injury.
Highlights
Eicosapentaenoic acid (EPA) is a -3 polyunsaturated fatty acid with antiinflammatory and anti-cachetic properties that may have potential benefits with regards to skeletal muscle atrophy conditions where inflammation is present
EPA alone, either administered as a 2 h pre-treatment in differentiation media (DM), or continuously throughout the duration of the experiment, had no apparent effect on the normal pattern of myogenesis; myotubes were formed, their rate of differentiation was similar to controls and they appeared morphologically indistinct from controls; the timing of the appearance of myosin heavy chain (MyHC) and its pattern of expression as visualised by immunocytochemistry, was similar to that of controls
Since tumour necrosis factor (TNF)-α-induced apoptosis is associated with caspase-8 activation, by mechanisms downstream of the TNF-α receptor 1 (TNFR1) in differentiating myoblasts [18,19,28], we evaluated caspase-8 activity in response to treatment with TNF-α, and with EPA to determine whether EPA could block the caspase-8 activity associated with TNF-α-induced apoptosis
Summary
Eicosapentaenoic acid (EPA) is a -3 polyunsaturated fatty acid with antiinflammatory and anti-cachetic properties that may have potential benefits with regards to skeletal muscle atrophy conditions where inflammation is present. It is reported that pathologic levels of the pro-inflammatory cytokine tumour necrosis factor (TNF)-α 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-α. Inflammation has been suggested to be present in a number of disease states associated with muscle atrophy, such as cancer, heart failure, rheumatoid arthritis, chronic obstructive pulmonary disease, HIV/AIDS, and ageing related muscle wasting Associated with this response are pro-inflammatory cytokines, such as tumour necrosis factor (TNF)-α that are commonly present at elevated levels (0.5–10 ng/ml) during disease[2,3,4,5]. A more recent finding suggests differentiated (C2C12) myotubes are susceptible to TNF-α-mediated apoptosis [17]
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