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

Abstract

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-κB (NF-κB). Notably, the 18-carbon PUFAs did not reverse LPS-induced atrophy in C2C12 myotubes transfected with a constitutively active mutant IκB kinase-β plasmid, which suggests the importance of the inhibition of NF-κB 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.