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Journal of Lipid Research, Vol. 48, 1966-1975, September 2007
Copyright © 2007 by American Society for Biochemistry and Molecular Biology

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

Francesco Natali^*, Luisa Siculella^*, Serafina Salvati and Gabriele V. Gnoni^1,*

^* Laboratory of Biochemistry and Molecular Biology, Department of Biological and Environmental Sciences and Technologies, University of Salento, 73100 Lecce, Italy
Food Science, Nutrition, and Health Department, Istituto Superiore di Sanità, 00161 Rome, Italy

Published, JLR Papers in Press, June 13, 2007.

¹ To whom correspondence should be addressed. e-mail: 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 at depressing lipogenesis and cholesterologenesis; a decreased label incorporation into cellular palmitic, stearic, and oleic acids was detected, suggesting that an enzymatic step(s) of de novo fatty acid biosynthesis was affected. To clarify this issue, the activities of acetyl-coenzyme A carboxylase (ACC) and 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, whereas 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 decreases in ACC and HMGCR mRNA abundance and protein levels. The downregulation of ACC and HMGCR activities and expression by oleic acid could contribute to the reduced lipogenesis and cholesterologenesis.

Supplementary key words acetyl-coenzyme A carboxylase • cholesterologenesis • fatty acid synthase • 3-hydroxy-3-methylglutaryl coenzyme A reductase • lipogenensis

Abbreviations: ACC, acetyl-coenzyme A carboxylase; HMGCR, 3-hydroxy-3-methylglutaryl coenzyme A reductase; MTT, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide

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