Effect of exogenous fatty acids on lipid synthesis, marker‐enzymes, and development of glial cells maintained in serum‐free culture

Sykes, Jane E.; Lopes‐Cardozo, M.

doi:10.1002/glia.440030608

Cited by 4 publications

(2 citation statements)

References 40 publications

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“…Several investigations have shown an abnormally active synthesis of cholesterol from acetate in malignant glial cells compared with their normal counterparts (43,44). The inhibition of HMGCR activity and expression by exogenous fatty acids reported in this study adds further support to previous findings (46,47), indicating that fatty acids exogenously added to C6 cells may represent specific means of controlling gliomatous growth.…”

Section: Discussionsupporting

confidence: 88%

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

Natali

Siculella

Salvati

et al. 2007

Journal of Lipid Research

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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 [1-14 C]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 acetylcoenzyme 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.-Natali, F., L. Siculella, S. Salvati, and G. V. Gnoni. Oleic acid is a potent inhibitor of fatty acid and cholesterol synthesis in C6 glioma cells. J. Lipid Res. 2007Res. . 48: 1966Res. -1975. After white adipose tissue, the brain is the organ with the highest lipid content of the body. The biosynthesis and deposition of lipids play an important role in maintaining brain structure and function, for example, during development-associated biogenesis of neural cell membranes. It is well established that alterations in lipid metabolism are the cause of or are associated with many neurological diseases (1-3).Astrocytes, the major class of glial cells in the mammalian brain, play an active role in brain metabolism. These cells surround intraparenchymal blood capillaries so that they represent the first cellular barrier for nutrients and other substances entering the brain system. A metabolic coupling between astrocytes and neurons to maintain energy metabolism homeostasis has been described (4, 5). Metabolic regulation in the brain has been investigated extensively, and those studies focused mostly on carbohydrate and amino acid metabolism (for review, see Ref. 6). During neuronal activity, glucose taken up by astrocytes is converted into lactate, which is then released into the extracellular space to be used by neurons (6). Regarding lipid metabolism, astroglial ketone body synthesis, showing characteristics strikingly similar to those of hepatic ketogenesis (7), may represent an important pathway for brain energy production and/or biosynthetic processes. The involvement of fatty acids in cell death pathways, particularly in the con...

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Section: Discussionsupporting

confidence: 88%

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

Natali

Siculella

Salvati

et al. 2007

Journal of Lipid Research

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“…Thus, the remarkable decrease we observed in the present study of the phospholipids and cholesterol syntheses exerted by OA and HTyr led us to suppose that EVOO components might modulate in C6 cells the shift towards membrane biogenesis instead of an accumulation of cellular neutral lipids. Actually, this hypothesis is corroborated by previous studies which indicated that fatty acids exogenously added to C6 cells may represent specific means of controlling gliomatous growth [ 5 , 43 , 44 ].…”

Section: Discussionsupporting

confidence: 73%

Oleic Acid and Hydroxytyrosol Inhibit Cholesterol and Fatty Acid Synthesis in C6 Glioma Cells

Priore

Gnoni

Natali

et al. 2017

Oxidative Medicine and Cellular Longevity

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Recently, the discovery of natural compounds capable of modulating nervous system function has revealed new perspectives for a healthier brain. Here, we investigated the effects of oleic acid (OA) and hydroxytyrosol (HTyr), two important extra virgin olive oil compounds, on lipid synthesis in C6 glioma cells. OA and HTyr inhibited both de novo fatty acid and cholesterol syntheses without affecting cell viability. The inhibitory effect of the individual compounds was more pronounced if OA and HTyr were administered in combination. A reduction of polar lipid biosynthesis was also detected, while triglyceride synthesis was marginally affected. To clarify the lipid-lowering mechanism of these compounds, their effects on the activity of key enzymes of fatty acid biosynthesis (acetyl-CoA carboxylase-ACC and fatty acid synthase-FAS) and cholesterologenesis (3-hydroxy-3-methylglutaryl-CoA reductase-HMGCR) were investigated in situ by using digitonin-permeabilized C6 cells. ACC and HMGCR activities were especially reduced after 4 h of 25 μM OA and HTyr treatment. No change in FAS activity was observed. Inhibition of ACC and HMGCR activities is corroborated by the decrease of their mRNA abundance and protein level. Our results indicate a direct and rapid downregulatory effect of the two olive oil compounds on lipid synthesis in C6 cells.

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Arachidonic acid as a neurotoxic and neurotrophic substance

Katsuki

Okuda

1995

Progress in Neurobiology

276

210

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Effect of exogenous fatty acids on lipid synthesis, marker‐enzymes, and development of glial cells maintained in serum‐free culture

Cited by 4 publications

References 40 publications

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

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

Oleic Acid and Hydroxytyrosol Inhibit Cholesterol and Fatty Acid Synthesis in C6 Glioma Cells

Arachidonic acid as a neurotoxic and neurotrophic substance

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