Anti-inflammatory effects of Omega 3 fatty acids on murine skeletal muscle cell differentiation
Year: 2011
Type: dissertation
Abstract: Eicosapentaenoic acid (ERA) is an w-3 polyunsaturated fatty acid \n(PUFA) with anti-inflammatory and anti-cachetic properties. \nThese properties have not previously been investigated \nsimultaneously with regards to skeletal muscle damage and \nregeneration and therefore the main aim of this work was to \nexamine the possible protective effects of ERA during damage \ninduced by the pro-inflammatory cytokines TNF-a and TWEAK . \nUsing an established model of myoblast differentiation, skeletal \nmuscle cell differentiation was shown to be morphologically \nimpaired by TNF-a and TWEAK. Formation of myotubes was \nrestricted as shown by reduced myoblast fusion indices (Ml) and \nmyotube widths. These effects were associated with TNF-a \ninduced apoptosis. Both cytokines caused increased expression \nof pro-inflammatory gene targets of NF-KB activity; TNF-a and IL- \n6 and in parallel, TNF-a treatment increased NF-KB activity and \ninhibited expression and activation of PPARy. \nEPA prevented the TWEAK /TNF-mediated loss of expression \nMyHC expression (reduced to 5-30% Ml) and significantly \nincreased myogenic fusion (p<0.05) and myotube diameter \n(p<0.05) indices back to control levels (Back to approx 70% Ml). \nERA protective activity was associated with blocking cell death \npathways as ERA completely attenuated TNF-mediated \nincreases in caspase-8 activity (p<0.05) and cellular \nnecrosis/apoptosis (p<0.05) back to their respective control \nlevels. This led to investigation of the possible mechanisms of \naction for ERA using the TNF-a damage model. ERA blocked NFKB \nactivation, downstream gene targets of NF-KB activity, IL-6 \nand TNF-a, and was associated with upregulation and activation \nof PPARv. Pre-treatment with a specific PPARy antagonist \n(GW9662) inhibited these actions of ERA, thus confirming that \nERA activity was at least partially dependent on PPARy. \nThis thesis has shown for the first time that PUFA such as ERA \npromote skeletal muscle differentiation in opposition to \npathological levels of inflammatory cytokines. Thus, PUFAs such \nas ERA may represent a class of naturally occurring, low toxicity, \nPPAR ligands that could have clinical applications for treatment \nof inflammation-associated ongoing skeletal muscle damage in \nchronic disease states or ageing.
Author: Peter Magee
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W1483191972