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Hydroxytyrosol stimulates lipolysis via A-kinase and extracellular signal-regulated kinase activation in 3T3-L1 adipocytes

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Abstract

Purpose

The principal function of the adipose tissue is the storage of energy in the form of triglyceride through the process of adipogenesis, as well as the provision of the stored energy through lipolysis. In the present study, we investigated the effect of hydroxytyrosol on lipolysis in 3T3-L1 adipocytes.

Methods

3T3-L1 adipocytes, used as in vitro model in this study, were treated with several concentration of hydroxytyrosol. Glycerol release was measured to identify the lipolytic rate activation. All factors activation and expression were carried out via Western blotting and qRT-PCR.

Results

Our results showed that hydroxytyrosol, over a range of concentrations, attenuated triglyceride accumulation and stimulated glycerol release in fully differentiated adipocytes in a dose- and time-dependent manner. Moreover, hydroxytyrosol had no effect on adipocyte viability. To understand the mechanism underlying hydroxytyrosol-stimulated lipolysis, we used inhibitors of PKA, PKC, PKG, ERK1/2, and nitric oxide production. Pretreatment with a PKA inhibitor (Rp-cAMPs) and an ERK1/2 inhibitor (U0126) significantly attenuated hydroxytyrosol-stimulated lipolysis. In contrast, a PKC inhibitor (Calphostin C), 2 PKG inhibitors (KT 5823 and Rp-cGMPs), and a nitric oxide inhibitor (S-ethyl ITU) had no effect on hydroxytyrosol-stimulated lipolysis. Over the same range of concentrations, hydroxytyrosol downregulated the expression of adipose triglyceride lipase, hormone sensitive lipase (HSL), and adipogenesis-related transcription factors PPARγ and C/EBPα. In addition, hydroxytyrosol increased the phosphorylation rate of HSL at Ser563 and Ser660, as well as perilipin and ERK phosphorylation.

Conclusion

Hydroxytyrosol induced lipolysis in 3T3-L1 adipocytes via the activation of PKA and ERK1/2 pathway.

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Acknowledgments

This work was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Science, Sports, and Culture of Japan and a scholarship grant from the Ministry of Higher Education, Scientific Research and Technology of Tunisia. All opinions, findings, conclusions, and recommendations expressed in this publication are those of the author(s).

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

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Authors and Affiliations

  1. Faculty of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki, 305-8572, Japan

    Riadh Drira & Kazuichi Sakamoto

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  1. Riadh Drira
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  2. Kazuichi Sakamoto
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Correspondence to Kazuichi Sakamoto.

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Drira, R., Sakamoto, K. Hydroxytyrosol stimulates lipolysis via A-kinase and extracellular signal-regulated kinase activation in 3T3-L1 adipocytes. Eur J Nutr 53, 743–750 (2014). https://doi.org/10.1007/s00394-013-0578-7

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  • DOI: https://doi.org/10.1007/s00394-013-0578-7

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