Conjugated linoleic acid isomers anti-neuroinflammatory effects on activated microglial cells

Conjugated linoleic acid (CLA) isomers display anti-inflammatory effects within the central nervous system (CNS). This research examined how CLA isomers c9,t11 and t10,c12 influence fatty acid (FA) and N-acylethanolamine (NAE) profiles, along with their relationship with the expression of pro-inflammatory molecules in the BV-2 microglia cell line, which are the resident immune cells in the CNS that play a key role in sustaining neuronal activity and immune balance. BV-2 cells were exposed to 25 μM of c9,t11-CLA, t10,c12-CLA, or oleic acid (OA) for 24 hours, after which they were stimulated with lipopolysaccharide (LPS). Following the treatment, the fatty acid and N-acylethanolamine profiles, as well as the expression of pro-inflammatory molecules, were assessed. Our findings showed that CLA isomers lessen the morphological alterations caused by LPS in BV-2 cells and decrease both the gene expression and protein levels of inflammatory markers. This impact was associated with an increase in acyl-CoA oxidase 1, an important enzyme involved in the anti-inflammatory peroxisomal beta-oxidation pathway that effectively processes CLA isomers. Importantly, t10,c12-CLA markedly inhibited stearoyl-CoA desaturase 1, which influenced the production of monounsaturated fatty acids. The profile of NAEs was significantly modified by CLA isomers, leading to a notable increase in the release of the anti-neuroinflammatory mediator known as docosahexaenoic acid (DHA)-derived N-acylethanolamine (DHAEA). In summary, our research indicates that the anti-neuroinflammatory properties of CLA isomers can be attributed to their effects on fatty acid metabolism and modulation of bioactive fatty acid-derived N-acylethanolamines, emphasizing a potential approach for nutritional interventions in conditions marked by neuroinflammation.