18-Carbon polyunsaturated fatty acids via down-regulation NF-κB activation reduce lipopolysaccharide-induced myotube atrophy

Muscle atrophy often occurs in cachexia of various inflammation-related diseases. Systemic inflammation and the inflammatory pathway contribute to cachexia-induced muscle atrophy, which is associated with activation of two major protein degradation systems, the ubiquitin-proteasome pathway (UPP) and the autophagy-lysosomal pathway (ALP). The aim of this study was to explore the effects of linoleic acid, alpha-linolenic acid, and gamma-linolenic acid, 18-carbon polyunsaturated fatty acids (PUFAs), on lipopolysaccharide (LPS)-induced myotube atrophy and possible mechanisms of these actions. Our data demonstrated that these three test 18-carbon PUFAs significantly inhibited LPS-induced C2C12 myotube atrophy as well as activation of UPP and ALP, as evidenced by decreases in LPS-induced expression of muscle-specific ring finger protein 1, protein ubiquitination, and microtubule-associated protein 1 light chain 3B. Moreover, the 18-carbon PUFAs diminished LPS-induced expression of pro-inflammatory cytokines and phosphorylated mitogen-activated protein kinases as well as the transcriptional activity of nuclear factor-kappa B (NF-kappa B). Notably, the 18-carbon PUFAs did not reverse LPS-induced atrophy in C2C12 myotubes transfected with a constitutively active mutant I kappa B kinase-beta plasmid, which suggests the importance of the inhibition of NF-kappa B activation by the 18-carbon PUFAs. Our findings suggest that the 18-carbon PUFAs are beneficial for improving cachexia-induced myotube atrophy in inflammation-related diseases.