Endocrine Abstracts

Introduction: Sarcopenic obesity prevails with ageing, encompassing excess weight gains and muscle mass or strength losses. Free fatty acids and proinflammatory cytokines are elevated in obese adults. Palmitate decreases the anabolic effects of IGF signalling, while EPA elicits anti-inflammatory activities.

We aimed to examine the effects of palmitate and EPA on TNF-α/IGF1 interactions in established models of skeletal muscle cell loss.

Methods and results: Palmitate (750 μM) pretreatment increased myoblast death by >50% versus controls (P<0.05) and reduced myoblast differentiation by 84% versus IGF1 (97±7 vs 600±29 CK Units/mg; P<0.05). By contrast, TNF-α (10 ng/ml) induced myoblast apoptosis was reduced by co-incubation with EPA (50 μM; 26±2 vs 14±3%; P<0.05). Although basal and IGF-induced myoblast differentiation were significantly (P<0.05) increased by EPA (572±27 vs 782±32 basal and 600±29 vs 800±24 Units/mg IGF1), it could not rescue TNF-α induced (1.25 and 10 ng/ml) inhibition of differentiation. IGFBP5, IGF2, MyoD and myogenin mRNA expression were significantly (P<0.05) down-regulated by palmitate versus EPA pre-administration (97±18; 68±11; 70±16; 84±27%, respectively) but were not significantly different between control and EPA. Expression of Id3, an inducer of proliferation and hence inhibitor of differentiation, was increased 6-fold (P<0.05) by palmitate at 72-h compared with control. Critically, co-administration of palmitate and EPA significantly dampened the negative effects of palmitate, increasing myoblast survival and differentiation. Although still down-regulated palmitate/EPA co-treatment increased IGFBP5 and myogenin levels by 89±28 and 54±15% respectively relative to palmitate alone but IGF2, MyoD and Id3 levels remained unchanged.

Conclusion: Palmitate-induced myoblast apoptosis and inhibition of differentiation is associated with elevated Id3 and reduced IGFBP5, IGF2, MyoD and myogenin expression. EPA elicits protective action against the apoptotic effects not only of TNF-α but also of palmitate. These findings encourage investigations of the potential therapeutic effects of EPA in inflammatory conditions, such as sarcopenic obesity.