Oleuropein Induces AMPK-Dependent Autophagy in NAFLD Mice, Regardless of the Gender
Open accessAbstract
Oleuropein (Ole) is one of the most plentiful phenolic compounds with antioxidant, anti-inflammatory, anti-atherogenic, hypoglycemic and hypolipidemic effects. The aim of our study was to establish whether the positive Ole-related effects on liver steatosis could be associated with autophagy. Female and male C57BL/6J mice were fed normal diet (ND) or high-fat diet (HFD) for eight weeks, and Ole was added or not for the following eight weeks. The autophagy-related proteins Akt, mTOR, AMPK, ULK1, Beclin-1, LC3B and p62/Sqstm1 were analyzed. Interestingly, Ole induced a different regulation of the Akt/mTOR pathway in female compared to male mice, but was able to activate the autophagic process in ND and HFD mice through AMPK-dependent phosphorylation of ULK1 at Ser555, regardless of the gender. Our work reveals the ability of Ole to induce, in liver of ND and HFD mice, autophagy independently by gender-specific mTOR activation. We highlight Ole as a novel therapeutic approach to counteract unhealthy diet-related liver steatosis by targeting autophagy.
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Oleuropein promotes phosphorylation and activation of mitophagy-related proteins via the AMPK-ULK1 pathway in a diet-induced mouse model of obesity.
“Finally, oleuropein, a polyphenol present in the leaves of fruits and olives, promotes phosphorylation and consequent activation of mitophagy-related proteins by activation of the AMPK–ULK1 pathway in a diet-induced mouse model of obesity235.”
From Mitochondrial and metabolic dysfunction in ageing and age-related diseases (2022) · cites this paper as [235]
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Epigenetic Regulations by Olive Bioactives: Targeting HDAC for Disease Prevention and Therapy
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- Authors
- Porcu, C., Sideri, S., Martini, M., Cocomazzi, A., Galli, A., Tarantino, G., & Balsano, C.
- Affiliations
- University of L'Aquila (IT)
- Università Cattolica del Sacro Cuore (IT)
- University of Florence (IT)
- Federico II University Hospital (IT)
- Corresponding author
- Balsano, Clara
- ORCID
- Venue
- International Journal of Molecular Sciences
- Publisher
- MDPI AG
- Published
- 2018-12-08
- Volume
- 19
- Issue
- 12
- Pages
- 3948
- ISSN
- 1422-0067 (ISSN-L)
- PMC
- PMC6321282
- OpenAlex
- W2904933936
- Cited by
- 58
- References
- 44
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 8 · 2023: 7 · 2022: 6 · 2021: 7 · 2020: 8 · 2019: 7
- FWCI
- 4.29
- Type
- journal article
- Language
- en
- Open access
- gold
- dx.doi.org
- Licence
- Locations
- International Journal of Molecular Sciences (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Florence Research (University of Florence) (submittedVersion, other-oa)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion, other-oa)
- Archivio Istituzionale della Ricerca - Università degli Studi dell Aquila (submittedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Physical Sciences › Chemistry › Organic Chemistry › Edible Oils Quality and Analysis
- Keywords
- oleuropein, autophagy, non-alcoholic fatty liver disease, hepatic steatosis, AMPK, ULK1 phosphorylation, Akt/mTOR signaling, sex differences, high-fat diet, Beclin-1, LC3B, p62, phenolic compounds
- MeSH terms
- Autophagy-Related Protein-1 Homolog, Animals, Autophagy, Enzyme Activation, Female, Liver, Male, Mice, Inbred C57BL, Transcription, Genetic, Signal Transduction, Apoptosis, Proto-Oncogene Proteins c-bcl-2, Iridoids, Caspase 3, AMP-Activated Protein Kinases, Iridoid Glucosides, TOR Serine-Threonine Kinases, Diet, High-Fat, Non-alcoholic Fatty Liver Disease
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