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Int. J. Mol. Sci. 2018, 19(12), 3948; https://doi.org/10.3390/ijms19123948

Oleuropein Induces AMPK-Dependent Autophagy in NAFLD Mice, Regardless of the Gender

1
F. Balsano Foundation, Via Giovanni Battista Martini 6, 00198 Rome, Italy
2
MESVA Department, University of L’Aquila, Piazza S. Salvatore Tommasi 1, 67100 Coppito, L’Aquila, Italy and F. Balsano Foundation, Via Giovanni Battista Martini 6, 00198 Rome, Italy
3
Fondazione Policlinico A. Gemelli, IRCCS, Università Cattolica del Sacro Cuore Rome, Italy
4
Gastroenterology Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, 50139 Florence, Italy
5
Department of Clinical Medicine and Surgery, Federico II University Medical School of Naples, 80131 Naples, Italy
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 13 September 2018 / Revised: 30 November 2018 / Accepted: 7 December 2018 / Published: 8 December 2018
(This article belongs to the Special Issue Olive Bioactives, Nutraceuticals and Health)
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Abstract

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. View Full-Text
Keywords: autophagy; AMPK; mTOR; oleuropein; phenolic compound; nutraceutical; Mediterranean diet; olive oil; liver steatosis; NAFLD autophagy; AMPK; mTOR; oleuropein; phenolic compound; nutraceutical; Mediterranean diet; olive oil; liver steatosis; NAFLD
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Porcu, C.; Sideri, S.; Martini, M.; Cocomazzi, A.; Galli, A.; Tarantino, G.; Balsano, C. Oleuropein Induces AMPK-Dependent Autophagy in NAFLD Mice, Regardless of the Gender. Int. J. Mol. Sci. 2018, 19, 3948.

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