title: Extra virgin olive oil phenols down-regulate lipid synthesis in primary-cultured rat-hepatocytes.
abstract: Hydroxytyrosol, tyrosol, and oleuropein, the main phenols present in extra virgin olive oil, have been reported to exert several biochemical and pharmacological effects. Here, we investigated the short-term effects of these compounds on lipid synthesis in primary-cultured rat-liver cells. Hydroxytyrosol, tyrosol and oleuropein inhibited both de novo fatty acid and cholesterol syntheses without an effect on cell viability. The inhibitory effect of individual compounds was already evident within 2 h of 25 μM phenol addition to the hepatocytes. The degree of cholesterogenesis reduction was similar for all phenol treatments (-25/30%), while fatty acid synthesis showed the following order of inhibition: hydroxytyrosol (-49%) = oleuropein (-48%) > tyrosol (-30%). A phenol-induced reduction of triglyceride synthesis was also detected. To clarify the lipid-lowering mechanism of these compounds, their influence on the activity of key enzymes of fatty acid biosynthesis (acetyl-CoA carboxylase and fatty acid synthase), triglyceride synthesis (diacylglycerol acyltransferase) and cholesterogenesis (3-hydroxy-3-methyl-glutaryl-CoA reductase) was investigated in situ by using digitonin-permeabilized hepatocytes. Acetyl-CoA carboxylase, diacylglycerol acyltransferase and 3-hydroxy-3-methyl-glutaryl-CoA reductase activities were reduced after 2 h of 25 μM phenol treatment. No change in fatty acid synthase activity was observed. Acetyl-CoA carboxylase inhibition (hydroxytyrosol, -41%, = oleuropein, -38%, > tyrosol, -17%) appears to be mediated by phosphorylation of AMP-activated protein kinase. These findings suggest that a decrease in hepatic lipid synthesis may represent a potential mechanism underlying the reported hypolipidemic effect of phenols of extra virgin olive oil.
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, Department of Biological and Environmental Sciences and Technologies, University of Salento, Via Prov.le Lecce-Monteroni, 73100 Lecce, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Priore
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, Department of Biological and Environmental Sciences and Technologies, University of Salento, Via Prov.le Lecce-Monteroni, 73100 Lecce, Italy. Electronic address: luisa.siculella@unisalento.it.
authors.forename: Luisa
authors.initials: L
authors.lastname: Siculella
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, Department of Biological and Environmental Sciences and Technologies, University of Salento, Via Prov.le Lecce-Monteroni, 73100 Lecce, Italy.
authors.forename: Gabriele Vincenzo
authors.initials: GV
authors.lastname: Gnoni
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000103:Acetyl-CoA Carboxylase / Q000037:antagonists & inhibitors; D000818:Animals; D002478:Cells, Cultured; D002784:Cholesterol / Q000096:biosynthesis; D051048:Diacylglycerol O-Acyltransferase / Q000037:antagonists & inhibitors; D015536:Down-Regulation; D005227:Fatty Acids / Q000096:biosynthesis*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D057888:Iridoid Glucosides; D039823:Iridoids / Q000494:pharmacology; D008055:Lipids / Q000096:biosynthesis*; D050155:Lipogenesis / Q000187:drug effects*; D008297:Male; D000069463:Olive Oil; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives / Q000494:pharmacology; D010766:Phosphorylation; D010938:Plant Oils / Q000494:pharmacology*; D017208:Rats, Wistar
chemical_list: D005227:Fatty Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D057888:Iridoid Glucosides; D039823:Iridoids; D008055:Lipids; D000069463:Olive Oil; D010938:Plant Oils; C005975:3,4-dihydroxyphenylethanol; C011867:4-hydroxyphenylethanol; C002769:oleuropein; D002784:Cholesterol; D051048:Diacylglycerol O-Acyltransferase; D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase; D010626:Phenylethyl Alcohol
keywords: AMP-activated protein kinase; Acetyl-CoA carboxylase; Extra virgin olive oil; Lipid synthesis; Phenols; Rat-hepatocytes