J. Lipid Res. Neurobiology of Lipids (ISSN1683-5506)
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A more recent version of this article appeared on September 1, 2007

Papers In Press, published online ahead of print June 13, 2007
J. Lipid Res., doi:10.1194/jlr.M700051-JLR200
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Submitted on January 29, 2007
Revised on June 7, 2007
Accepted on June 11, 2007

Oleic acid is a potent inhibitor of fatty acid and cholesterol syntheses in C6 glioma cells

Francesco Natali, Luisa Siculella, Serafina Salvati, and Gabriele V. Gnoni

Scienze e Tecnologie Biologiche ed Ambientali, Università di Lecce, Lecce, Lecce 73100

Corresponding Author: gabriele.gnoni{at}unile.it

Glial cells play a pivotal role in brain fatty acid metabolism and membrane biogenesis. However, the potential regulation of lipogenesis and cholesterologenesis by fatty acids in glial cells has been barely investigated. Here we show that physiologically relevant concentrations of various saturated, monounsaturated and polyunsaturated fatty acids significantly reduce [1-14C]acetate incorporation into fatty acids and cholesterol in C6 cells. Oleic acid was the most effective in depressing lipogenesis and cholesterologenesis; a decreased label incorporation into cellular palmitic, stearic and oleic acid was detected, suggesting that enzymatic step(s) of de novo fatty acid biosynthesis was affected. To clarify this issue, the activities of acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) were determined with an in situ digitonin-permeabilized cell assay after incubation of C6 cells with fatty acids. ACC activity was strongly reduced (~80%) by oleic acid, while no significant change in FAS activity was observed. Oleic acid also reduced the activity of 3-hydroxy-3-methylglutaryl Coenzyme A reductase (HMGCR). The inhibition of ACC and HMGCR activities is corroborated by the decrease in the ACC and HMGCR mRNA abundance and protein level. The down-regulation of ACC and HMGCR activity and expression by oleic acid could share in the reduced lipogenesis and cholesterologenesis.


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