Relevance of oleic acid and hydroxytyrosol, main compounds of extravirgin olive oil, in the inhibition of cholesterol and fatty acid biosyntheses in C6 glioma cells

Extra virgin olive oil (EVOO), the principal source of fat in the Mediterranean diet, positively affects human health, reducing the incidence of cancer, hypertension and cardiovascular diseases. Clinical studies support the efficacy of the EVOO also against the onset and progression of a number of neurodegenerative diseases. Brain fatty acid and cholesterol syntheses are critically challenged in several of these diseases. The finding that natural compounds are capable of modulating nervous system function has revealed new perspectives for an healthier brain. We investigated the effects of oleic acid (OA) and hydroxytyrosol (HTyr), two important EVOO compounds, on lipid synthesis in C6 glioma cells. Experimental data demonstrated that OA and HTyr inhibited within 4 h both de novo fatty acid and cholesterol syntheses; the inhibitory effect was more pronounced when OA and HTyr were administered in combination, revealing a synergic action. A remarkable reduction of polar lipids, but not of triglycerides biosynthesis was also observed in OA- and HTyrtreated C6 cells. The effects of OA and HTyr on the activity of the key enzymes of fatty acid biosynthesis, (acetyl-CoA carboxylase-ACC and fatty acid synthase-FAS) and cholesterologenesis (3-hydroxy-3-methyl-glutaryl-CoA reductase-HMGCR) were investigated in C6 cells. ACC and HMGCR activities were reduced by OA and HTyr treatment. No change in FAS activity was observed. The inhibition of ACC and HMGCR activities, observed in OA- and HTyr-treated C6 cells, is corroborated by the decrease in the corresponding mRNA abundance and protein level. Overall, our data indicate a direct and synergic effect of OA and HTyr on lipid synthesis in C6 cells. The modulation of the activity and expression of the key enzymes of lipid synthesis suggests a putative role of the two EVOO bioactive compounds in the prevention of several neurological diseases.