Soleus muscle contains a higher concentration of lipid metabolites than extensor digitorum longus in rats with lipopolysaccharide-induced acute muscle atrophy

BACKGROUND & AIMS:Muscle atrophy is one of the most important and frequent problems for critically ill patients. The purpose of this study was to evaluate the effect of lipid mediators on acute muscle atrophy. Skeletal muscle fiber-specific analysis of lipid mediators in endotoxemic rats was therefore performed. METHODS:Male Wistar rats were intraperitoneally injected with lipopolysaccharide (LPS). Slow-twitch soleus muscle and fast-twitch extensor digitorum longus (EDL) muscle were harvested 0, 6, and 24 h after LPS injection. Lipid mediators were profiled using liquid chromatography-tandem mass spectrometry, and free fatty acid (FFA) concentrations were measured using gas chromatography-mass spectrometry. Muscles were weighed and their cross-sectional areas were evaluated. Expression levels of mRNAs encoding inflammatory cytokines, autophagy-related transcription factors, and members of the ubiquitin-proteasome system were measured using real-time PCR. RESULTS:Before LPS injection, the concentrations of all FFAs, including arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid, and all measured lipid mediators were higher in soleus muscle than in EDL muscle, especially those of pro-inflammatory prostaglandin E2 (PGE2) and leukotriene B4. LPS injection, increased PGE2 and D2 and decreased FFAs in soleus muscle but did not change in EDL muscle. The concentrations of specialized pro-resolving mediators E-series hydroxy-eicosapentaenoic acid and D-series hydroxy-docosahexaenoic acid were higher in soleus muscle. Muscle cross-sectional area decreased and the expression level of atrogin-1 was upregulated in EDL muscle, but both were unchanged in soleus muscle. After LPS injection, a discrepancy involving an increased PGE2 concentration and decreased muscle atrophy was identified in this acute muscle atrophy model of critical illness. CONCLUSION:Concentrations of FFAs and lipid mediators were higher in soleus muscle than in EDL muscle, and LPS injection rapidly increased concentrations of pro-inflammatory lipid mediators. However, muscle atrophy with upregulation of autophagy-related transcription factors was observed in EDL muscle but not in soleus muscle.