Oleate Prevents Palmitate-Induced Atrophy via Modulation of Mitochondrial ROS Production in Skeletal Myotubes

Accumulation of saturated fatty acids contributes to lipotoxicity-related insulin resistance and atrophy in skeletal muscle. Conversely, unsaturated fatty acids like docosahexaenoic acid were proven to preserve muscle mass. However, it is not known if the most common unsaturated oleate will protect skeletal myotubes against palmitate-mediated atrophy, and its specific mechanism remains to be elucidated. Therefore, we investigated the effects of oleate on atrophy-related factors in palmitate-conditioned myotubes. Exposure of myotubes to palmitate, but not to oleate, led to an induction of fragmented nuclei, myotube loss, atrophy, and mitochondrial superoxide in a dose-dependent manner. Treatment of oleate to myotubes attenuated production of palmitate-induced mitochondrial superoxide in a dose-dependent manner. The treatment of oleate or MitoTEMPO to palmitate-conditioned myotubes led to inhibition of palmitate-induced mRNA expression of proinflammatory (TNF-α and IL6), mitochondrial fission (Drp1 and Fis1), and atrophy markers (myostatin and atrogin1). In accordance with the gene expression data, our immunocytochemistry experiment demonstrated that oleate and MitoTEMPO prevented or attenuated palmitate-mediated myotube shrinkage. These results provide a mechanism indicating that oleate prevents palmitate-mediated atrophy via at least partial modulation of mitochondrial superoxide production.