Anti-inflammatory effects of Omega 3 fatty acids on murine skeletal muscle cell differentiation

Magee, P

Abstract

Eicosapentaenoic acid (ERA) is an w-3 polyunsaturated fatty acid
(PUFA) with anti-inflammatory and anti-cachetic properties.
These properties have not previously been investigated
simultaneously with regards to skeletal muscle damage and
regeneration and therefore the main aim of this work was to
examine the possible protective effects of ERA during damage
induced by the pro-inflammatory cytokines TNF-a and TWEAK .
Using an established model of myoblast differentiation, skeletal
muscle cell differentiation was shown to be morphologically
impaired by TNF-a and TWEAK. Formation of myotubes was
restricted as shown by reduced myoblast fusion indices (Ml) and
myotube widths. These effects were associated with TNF-a
induced apoptosis. Both cytokines caused increased expression
of pro-inflammatory gene targets of NF-KB activity; TNF-a and IL-
6 and in parallel, TNF-a treatment increased NF-KB activity and
inhibited expression and activation of PPARy.
EPA prevented the TWEAK /TNF-mediated loss of expression
MyHC expression (reduced to 5-30% Ml) and significantly
increased myogenic fusion (p<0.05) and myotube diameter
(p<0.05) indices back to control levels (Back to approx 70% Ml).
ERA protective activity was associated with blocking cell death
pathways as ERA completely attenuated TNF-mediated
increases in caspase-8 activity (p<0.05) and cellular
necrosis/apoptosis (p<0.05) back to their respective control
levels. This led to investigation of the possible mechanisms of
action for ERA using the TNF-a damage model. ERA blocked NFKB
activation, downstream gene targets of NF-KB activity, IL-6
and TNF-a, and was associated with upregulation and activation
of PPARv. Pre-treatment with a specific PPARy antagonist
(GW9662) inhibited these actions of ERA, thus confirming that
ERA activity was at least partially dependent on PPARy.
This thesis has shown for the first time that PUFA such as ERA
promote skeletal muscle differentiation in opposition to
pathological levels of inflammatory cytokines. Thus, PUFAs such
as ERA may represent a class of naturally occurring, low toxicity,
PPAR ligands that could have clinical applications for treatment
of inflammation-associated ongoing skeletal muscle damage in
chronic disease states or ageing.

Citation

Magee, P. Anti-inflammatory effects of Omega 3 fatty acids on murine skeletal muscle cell differentiation. (Thesis). Salford : University of Salford

• Thesis Type: Thesis
• Deposit Date: Oct 3, 2012
• Award Date: Jan 1, 2011