@article{2987825,
    title = "The olive constituent oleuropein, as a PPARα agonist, markedly reduces serum triglycerides",
    author = "Malliou, F. and Andreadou, I. and Gonzalez, F.J. and Lazou, A. and Xepapadaki, E. and Vallianou, I. and Lambrinidis, G. and Mikros, E. and Marselos, M. and Skaltsounis, A.-L. and Konstandi, M.",
    journal = "The Journal of Nutritional Biochemistry",
    year = "2018",
    volume = "59",
    pages = "17-28",
    publisher = "ELSEVIER SCIENCE INC 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA",
    issn = "0955-2863",
    doi = "10.1016/j.jnutbio.2018.05.013",
    keywords = "cholesterol;  hormone sensitive lipase;  oleuropein;  peroxisome proliferator activated receptor alpha;  peroxisome proliferator activated receptor alpha agonist;  triacylglycerol;  iridoid;  lipid;  low density lipoprotein receptor;  luciferase;  oleuropein;  Pcsk9 protein, mouse;  peroxisome proliferator activated receptor alpha;  proprotein convertase 9;  triacylglycerol, adult;  animal experiment;  animal tissue;  Article;  cholesterol blood level;  controlled study;  drug mechanism;  enzyme activation;  gene expression;  homeostasis;  human;  human cell;  hypolipidemic activity;  in vitro study;  in vivo study;  ligand binding;  lipid liver level;  liver;  luciferase assay;  male;  molecular docking;  mouse;  nonhuman;  olive tree;  plant leaf;  protein expression;  real time polymerase chain reaction;  triacylglycerol blood level;  upregulation;  Western blotting;  white adipose tissue;  wild type mouse;  animal;  blood;  cell culture;  chemistry;  drug effect;  genetics;  inbred mouse strain;  liver cell;  metabolism;  mutant mouse strain;  olive tree, Adipose Tissue, White;  Animals;  Cells, Cultured;  Hepatocytes;  Homeostasis;  Iridoids;  Lipids;  Luciferases;  Male;  Mice, Inbred Strains;  Mice, Mutant Strains;  Molecular Docking Simulation;  Olea;  PPAR alpha;  Proprotein Convertase 9;  Receptors, LDL;  Triglycerides",
    abstract = "Oleuropein (OLE), a main constituent of olive, exhibits antioxidant and hypolipidemic effects, while it reduces the infarct size in chow- and cholesterol-fed rabbits. Peroxisome proliferator-activated receptor α (PPARα) has essential roles in the control of lipid metabolism and energy homeostasis. This study focused on the mechanisms underlying the hypolipidemic activity of OLE and, specifically, on the role of PPARα activation in the OLE-induced effect. Theoretical approach using Molecular Docking Simulations and luciferase reporter gene assay indicated that OLE is a ligand of PPARα. The effect of OLE (100 mg/kg, p.o., per day, ×6 weeks) on serum triglyceride (TG) and cholesterol levels was also assessed in adult male wild-type and Ppara-null mice. Molecular Docking Simulations, Luciferase reporter gene assay and gene expression analysis indicated that OLE is a PPARα agonist that up-regulates several PPARα target genes in the liver. This effect was associated with a significant reduction of serum TG and cholesterol levels. In contrast, OLE had no effect in Ppara-null mice, indicating a direct involvement of PPARα in the OLE-induced serum TG and cholesterol reduction. Activation of hormone-sensitive lipase in the white adipose tissue (WAT) and the liver of wild-type mice and up-regulation of several hepatic factors involved in TG uptake, transport, metabolism and clearance may also contribute in the OLE-induced TG reduction. In summary, OLE has a beneficial effect on TG homeostasis via PPARα activation. OLE also activates the hormone sensitive lipase in the WAT and liver and up-regulates several hepatic genes with essential roles in TG homeostasis. © 2018 Elsevier Inc."
}