The Olive Constituent Oleuropein, as a PPARα Agonist, Markedly Reduces Serum Triglycerides
Open accessAbstract
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.
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Oleuropein is a ligand of peroxisome proliferator-activated receptor-alpha (PPAR-α).
“Previous research has shown that oleuropein is a ligand of peroxisome proliferator-activated receptor-alpha (PPAR-α) [48].”
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- Authors
- Malliou, F., Andreadou, I., Gonzalez, F. J., Lazou, A., Xepapadaki, E., Vallianou, I., Lambrinidis, G., Mikros, E., Marselos, M., Skaltsounis, A.-L., & Konstandi, M.
- Affiliations
- University of Ioannina (GR)
- National and Kapodistrian University of Athens (GR)
- National Institutes of Health (US)
- Aristotle University of Thessaloniki (GR)
- University of Patras (GR)
- Corresponding author
- Konstandi, Maria
- ORCID
- Venue
- The Journal of Nutritional Biochemistry
- Publisher
- Elsevier BV
- Published
- 2018-09
- Volume
- 59
- Pages
- 17-28
- ISSN
- 0955-2863 (ISSN-L)
- PMC
- PMC6628917
- OpenAlex
- W2807428653
- Cited by
- 45
- References
- 71
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 6 · 2023: 5 · 2022: 2 · 2021: 11 · 2020: 5 · 2019: 6
- FWCI
- 1.96
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journal of Nutritional Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (ZIABC005708, ZIABC005562)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Physical Sciences › Chemistry › Organic Chemistry › Edible Oils Quality and Analysis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Paraoxonase enzyme and polymorphisms
- Keywords
- oleuropein, serum triglycerides, hypolipidemic effect, PPARα target genes, hormone-sensitive lipase, white adipose tissue, hepatic lipid metabolism, cholesterol, PPARalpha-null mice, molecular docking
- MeSH terms
- Proprotein Convertase 9, Animals, Cells, Cultured, Homeostasis, Lipids, Luciferases, Male, Mice, Inbred Strains, Mice, Mutant Strains, Receptors, LDL, Triglycerides, Hepatocytes, Olea, Iridoids, PPAR alpha, Adipose Tissue, White, Iridoid Glucosides, Molecular Docking Simulation
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