Docosahexaenoic acid prevents atrophy‐related signaling in palmitate‐treated myotubes

Abstract

Lipid accumulation promotes insulin resistance and dysfunctional protein metabolism in skeletal muscle, resulting in debilitating muscle atrophy. While the saturated fatty acid palmitate (PA) induces muscle insulin resistance and promotes apoptosis and atrophic signaling pathways, omega‐3 polyunsaturated fatty acids such as docosahexaenoic acid (DHA) improve insulin sensitivity and may attenuate activation of pathways that lead to atrophy. Therefore, the purpose of this study was to examine the effects of saturated and omega‐3 fatty acids on atrophy‐related signaling pathways in skeletal muscle cells with the hypothesis that DHA prevents the detrimental effects of PA. C2C12 myotubes were treated with 0.1mM DHA and/or 0.5mM PA for 48 h. Insulin (100nM; 15 min) was added to cells to activate signaling pathways. The expression of proteins involved in atrophic and apoptotic signaling pathways was examined by Western analysis. PA reduced myotube size and number. PA also reduced insulin‐stimulated Akt, MEK1/2, and Foxo3a phosphorylation plus induced caspase‐3 and actin‐fragmentation. All of these responses were blocked by the addition of DHA; DHA alone had minimal effects on these pathways. In conclusion, these data suggest that DHA protects C2C12 myotubes from activation of atrophic signaling pathways by high levels of saturated fatty acids by maintaining insulin survival signaling.Support: NIH DK007734