Quercetin inhibits fatty acid and triacylglycerol synthesis in rat-liver cells.

BACKGROUND: Quercetin plays a cardiovascular protective role because of its antioxidant capacity and ability to modulate dyslipidemia. As alterations in hepatic lipid synthesis are crucial to the regulation of serum lipid levels, we investigated the quercetin effect on lipogenesis in rat liver cells. MATERIALS AND METHODS: The effect of quercetin on the rate of synthesis of fatty acids, cholesterol, neutral lipids, phospholipids and very-low-density lipoproteins (VLDL) was investigated in rat hepatocyte suspensions following [1-(14)C]acetate incorporation into these lipid fractions. Enzyme activities of acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) as well as diacylglycerol acyltransferase (DGAT) and 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA-R), pace-setting steps of de novo fatty acid, triacylglycerol (TAG) and cholesterol synthesis respectively were assayed in digitonin-permeabilized hepatocytes. RESULTS: Within 30 min of quercetin addition to the hepatocytes, inhibition (IC50 approximately 25 microM) of fatty acid synthesis occurred. A reduction in label incorporation mainly into TAG was observed. Among neosynthesized fatty acids, palmitic acid formation was greatly reduced, suggesting that enzymatic step(s) of de novo fatty synthesis was affected. Only ACC activity was noticeably reduced, but no change in FAS activity was observed. DGAT activity was also inhibited. The decreased intracellular TAG content was paralleled by a reduction in acetate incorporation into VLDL-TAG. Conversely, cholesterol synthesis and HMG-CoA-R were not significantly affected by quercetin. CONCLUSIONS: In hepatocytes from normal rats, the quercetin-induced decrease in both de novo fatty acid and TAG synthesis, with a consequent reduction in VLDL-TAG formation, may represent a potential mechanism contributing to the reported hypotriacylglycerolemic effect of quercetin.

Resveratrol inhibits fatty acid and triacylglycerol synthesis in rat hepatocytes.

BACKGROUND: The putative role of resveratrol, a polyphenol present in grapes and other plants, in modulating dislypidemia, thus preventing cardiovascular diseases, is generally based on proliferating cell lines and in vivo studies in different pathological conditions. The aim of the present study was to investigate whether resveratrol plays a role on lipid biosynthesis in rat hepatocytes. MATERIALS AND METHODS: The effect of resveratrol on total rate of fatty acid, cholesterol and complex lipid synthesis, assayed by the incorporation of [1-(14)C]acetate into these lipid fractions, was investigated in rat hepatocyte suspensions. Enzyme activities of acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) as well as 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA-R), pace-setting steps of de novo fatty acid and cholesterol synthesis, respectively, were in situ measured in digitonin-permeabilized hepatocytes. RESULTS: Resveratrol-treated hepatocytes exhibited a short-term (30 min) inhibition (IC(50) approximately 25 microm) of total fatty acid synthesis from [1-(14)C]acetate. Among neosynthesized fatty acids, palmitic acid formation was mainly reduced, thus suggesting that enzymatic step(s) of de novo fatty acid synthesis was affected by resveratrol. In digitonin-permeabilized hepatocytes, only ACC activity was noticeably reduced, while no change in FAS activity was observed. A noticeable resveratrol-induced reduction of label incorporation into triacylglycerols was also detected. Conversely, cholesterol synthesis and HMG-CoA-R activity were unaffected by resveratrol. CONCLUSION: Results here reported show that in isolated hepatocytes from normal rats a resveratrol-induced short-term inhibition of fatty acid and triacylglycerol synthesis occurs. This finding may represent a potential mechanism contributing to the reported hypolipidemic effect of resveratrol.

Changes in lipid composition and lipogenic enzyme activities in liver of lambs fed omega-6 polyunsaturated fatty acids.

Twenty-four lambs (Ovis aries) were used in a 45-day finishing study to evaluate the effects of feeding diets high in linoleic acid (C(18:2), omega-6) on liver lipid composition and on lipogenic enzyme activities in subcellular fractions of liver. Lambs were fed either a 5% safflower oil (SO, high linoleic acid) supplemented diet or a control diet without added oil. SO feeding caused a reduction in the amount of serum and liver triacylglycerols and cholesterol, whereas the level of phospholipids in both tissues was hardly affected. In liver of SO-treated lambs an increase in the levels of C(18:2) and arachidonic acid (C(20:4), omega-6), together with a simultaneous decrease of saturated fatty acids, was observed. In comparison to rat liver, rather low activities of enzymes in the pathway for de novo fatty acid synthesis, i.e. acetyl-CoA carboxylase and fatty acid synthase, were found in lamb-liver cytosol. Both enzyme activities, as well as those of the NADPH-furnishing enzymes, were significantly reduced by SO feeding. In contrast, microsomal and especially mitochondrial fatty acid chain elongation activity, the latter being much higher than that of rat liver, were significantly increased in SO-treated lambs. In these animals, a stimulation of triangle up(9)-desaturase activity was observed in liver microsomes.