Extra virgin olive oil phenols down-regulate lipid synthesis in primary-cultured rat-hepatocytes |
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Affiliation: | 1. Metabolic and Cardiovascular Disease Laboratory, Group on Molecular and Cell Biology of Lipids, Alberta Diabetes and Mazankowski Heart Institutes, University of Alberta, Edmonton, AB, Canada;2. Department of Agricultural Food and Nutritional Science, University of Alberta, Edmonton, AB, Canada;3. Department of Plant Science, University of Saskatchewan, Saskatoon, SK, Canada;4. Department of Pediatrics, Group on Molecular and Cell Biology of Lipids, University of Alberta, AB, Canada;1. Shaanxi Engineering Research Center for Viti-Viniculture, College of Enology/College of Horticulture, Northwest A&F University, Yangling, Shaanxi 712100, China;2. College of Life Sciences and Enology, Taishan University, Taian, Shandong 271021, China;3. Heyang Experimental and Demonstrational Stations for Grape, Northwest A&F University, Heyang, Shaanxi 715300, China;1. Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari “Aldo Moro”, Bari 70124,Italy;2. Institute of Biomembrane and Bioenergetics, CNR, Bari, Italy |
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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. |
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