Oleuropein induces AMPK-dependent autophagy in NAFLD mice, regardless of the gender

Cristiana Porcu, Silvia Sideri, Maurizio Martini, Alessandra Cocomazzi, Andrea Galli, Giovanni Tarantino, Clara Balsano

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article number3948
JournalInternational Journal of Molecular Sciences
Issue number12
Publication statusPublished - Dec 1 2018


  • AMPK
  • Autophagy
  • Liver steatosis
  • Mediterranean diet
  • MTOR
  • Nutraceutical
  • Oleuropein
  • Olive oil
  • Phenolic compound

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry


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