Quercetin inhibition of SREBPs and ChREBP expression results in reduced cholesterol and fatty acid synthesis in C6 glioma cells. (December 2019)

• Record Type: Journal Article
• Authors: Damiano, Fabrizio; Giannotti, Laura; Gnoni, Gabriele V.; Siculella, Luisa; Gnoni, Antonio
• Is Part Of: International journal of biochemistry & cell biology. Volume 117(2019)
• Publication Date: 2019-12
• Subjects: 3-Hydroxy-3-methyl-glutaryl-CoA reductase -- Acetyl-CoA carboxylase 1 -- C6 glioma cells -- Cholesterol and fatty acid synthesis -- ChREBP and SREBPs -- Quercetin; Biochemistry -- Periodicals; Cytology -- Periodicals; Biochemistry -- Periodicals; Cell Biology -- Periodicals; Biochimie -- Périodiques; Cytologie -- Périodiques; Biochimie; Cytologie; Biochemistry; Cytology; Ressource Internet (Descripteur de forme); Périodique électronique (Descripteur de forme); Periodicals; 572.05
• DOI: 10.1016/j.biocel.2019.105618
• Languages: English
• ISSNs: 1357-2725

Abstract

Highlights: Quercetin rapidly inhibits cholesterol and fatty acid synthesis in C6 glioma cells. Quercetin reduces the activity of ACC1 and HMGCR. Quercetin acts at transcriptional level by decreasing expression of SREBPs and ChREBP. Abstract: Quercetin (Que), a widely distributed flavonoid in the human diet, exerts neuroprotective action because of its property to antagonize oxidative stress. Here, we investigated the effects of Que on lipid synthesis in C6 glioma cells. A rapid Que-induced inhibition of cholesterol and, to a lesser extent, of fatty acid synthesis from [1- 14 C]acetate was observed. The maximum decrease was detected at the level of palmitate, the end product of de novo fatty acid synthesis. The effect of Que on the enzyme activities of acetyl-CoA carboxylase 1 (ACC1) and fatty acid synthase (FAS), the two enzymes of this pathway, was investigated directly in situ in permeabilized C6 cells. An inhibitory effect on ACC1 was observed after 4 h of 25 μM Que treatment, while FAS activity was not affected. A reduction of polar lipid biosynthesis was also detected. A remarkable decrease of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) activity, regulatory enzyme of cholesterol synthesis, was evidenced. Expression studies demonstrated that Que acts at transcriptional level, by reducing the mRNA abundance and protein amount of ACC1 and HMGCR. Deepening the molecular mechanism, we found that Que decreased the expression of SREBP-1 and SREBP-2, transcriptional factors representing the main regulators of de novo fatty acid and cholesterol synthesis, respectively. Que also reduced the nuclear content of ChREBP, a glucose-induced transcription factor involved in the regulation of lipogenic genes. Our results represent the first evidence that a direct and rapid downregulatory effect of Que on cholesterol and de novo fatty acid synthesis is elicited in C6 cells.