show Abstracthide AbstractLipids are a class of molecules present in all cell types, which play important roles in cellular structure and energy storage. In the last few of decades, it has been reported that long-chain fatty acids are involved in several biological functions from transcriptional regulation to physiological processes. Several fatty acids have been both positively and negatively implicated in different biological processes in skeletal muscle and other tissues. No differentially expressed genes (DEGs, FDR 10%) were identified for linoleic acid (LA) or stearic acid (SA), only a few DEGs were identified for eicosapentaenoic acid (EPA, 5 DEGs), docosahexaenoic acid (DHA, 4 DEGs) and palmitic acid (PA, 123 DEGs), while large numbers of DEGs were identified for oleic acid (OA, 1,134 DEGs) and conjugated linoleic acid cis9 trans11 (CLA-c9t11, 872 DEGs). Functional annotation and functional enrichment from OA DEGs identified important genes and canonical pathways such as SCD, PLIN5, LDL-cholesterol, CPT1, oxidative phosphorylation, insulin receptor signaling, docosahexaenoic acid (DHA) signaling, oleate biosynthesis and PPAR signaling associated. The top five canonical pathways identified from the list of DEGs for CLA-c9t11 were protein ubiquitination, interferon signaling, hypoxia signaling in the cardiovascular system, angiopoietin signaling and mTOR signaling. Surprisingly the variation in only a few of fatty acids was associated with differences in gene expression in skeletal muscle. These results indicate that only a couple fatty acids appear to have direct or indirect effects on skeletal muscle and possibly other tissues. This method could be utilized to evaluate the potential bioactivity of any cellular entity, e.g. proteins, metabolites, to help elucidate molecular mechanisms.